Journal articles on the topic 'N- and T-type calcium ion channels'
To see the other types of publications on this topic, follow the link: N- and T-type calcium ion channels.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'N- and T-type calcium ion channels.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Smith, Carolyn L., Salsabil Abdallah, Yuen Yan Wong, Phuong Le, Alicia N. Harracksingh, Liana Artinian, Arianna N. Tamvacakis, Vincent Rehder, Thomas S. Reese, and Adriano Senatore. "Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue." Journal of General Physiology 149, no. 4 (March 22, 2017): 483–510. http://dx.doi.org/10.1085/jgp.201611683.
Full textAbstract:
Four-domain voltage-gated Ca2+ (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells. Here, we characterize the single T-type calcium channel from Trichoplax adhaerens (TCav3), an early diverging animal that lacks muscle, neurons, and synapses. Co-immunolocalization using antibodies against TCav3 and neurosecretory cell marker complexin labeled gland cells, which are hypothesized to play roles in paracrine signaling. Cloning and in vitro expression of TCav3 reveals that, despite roughly 600 million years of divergence from other T-type channels, it bears the defining structural and biophysical features of the Cav3 family. We also characterize the channel’s cation permeation properties and find that its pore is less selective for Ca2+ over Na+ compared with the human homologue Cav3.1, yet it exhibits a similar potent block of inward Na+ current by low external Ca2+ concentrations (i.e., the Ca2+ block effect). A comparison of the permeability features of TCav3 with other cloned channels suggests that Ca2+ block is a locus of evolutionary change in T-type channel cation permeation properties and that mammalian channels distinguish themselves from invertebrate ones by bearing both stronger Ca2+ block and higher Ca2+ selectivity. TCav3 is the most divergent metazoan T-type calcium channel and thus provides an evolutionary perspective on Cav3 channel structure–function properties, ion selectivity, and cellular physiology.
2
Smith, Marianne R., Alexandra B. Nelson, and Sascha du Lac. "Regulation of Firing Response Gain by Calcium-Dependent Mechanisms in Vestibular Nucleus Neurons." Journal of Neurophysiology 87, no. 4 (April 1, 2002): 2031–42. http://dx.doi.org/10.1152/jn.00821.2001.
Full textAbstract:
Behavioral reflexes can be modified by experience via mechanisms that are largely unknown. Within the circuitry for the vestibuloocular reflex (VOR), neurons in the medial vestibular nucleus (MVN) show adaptive changes in firing rate responses that are correlated with VOR gain (the ratio of evoked eye velocity to input head velocity). Although changes in synaptic strength are typically assumed to underlie gain changes in the VOR, modulation of intrinsic ion channels that dictate firing could also play a role. Little is known, however, about how ion channel function or regulation contributes to firing responses in MVN neurons. This study examined contributions of calcium-dependent currents to firing responses in MVN neurons recorded with whole cell patch electrodes in rodent brain stem slices. Firing responses were remarkably linear over a wide range of firing rates and showed modest spike frequency adaptation. Firing response gain, the ratio of evoked firing rate to input current, was reduced by increasing extracellular calcium and increased either by lowering extracellular calcium or with antagonists to SK- and BK-type calcium-dependent potassium channels and N- and T-type calcium channels. Blockade of SK channels occluded gain increases via N-type calcium channels, while blocking BK channels occluded gain increases via presumed T-type calcium channels, indicating specific coupling of potassium channels and their calcium sources. Selective inhibition of Ca2+/calmodulin-dependent kinase II and broad-spectrum inhibition of phosphatases modulated gain via BK-dependent pathways, indicating that firing responses are tightly regulated. Modulation of firing response gain by phosphorylation provides an attractive mechanism for adaptive control of VOR gain.
3
Zhang, Weihua, Changqing Xu, Guangdong Yang, Lingyun Wu, and Rui Wang. "Interaction of H2S with Calcium Permeable Channels and Transporters." Oxidative Medicine and Cellular Longevity 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/323269.
Full textAbstract:
A growing amount of evidence has suggested that hydrogen sulfide (H2S), as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H2S and calcium ion channels and transporters, such as L-type calcium channels (LTCC), T-type calcium channels (TTCC), sodium/calcium exchangers (NCX), transient receptor potential (TRP) channels,β-adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR) in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H2S controls intracellular calcium homeostasis and the underlying mechanisms.
4
Polo-Parada, Luis, and Stephen J. Korn. "Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium." Journal of General Physiology 109, no. 6 (June 1, 1997): 693–702. http://dx.doi.org/10.1085/jgp.109.6.693.
Full textAbstract:
L-type Ca2+ channels select for Ca2+ over sodium Na+ by an affinity-based mechanism. The prevailing model of Ca2+ channel permeation describes a multi-ion pore that requires pore occupancy by at least two Ca2+ ions to generate a Ca2+ current. At [Ca2+] < 1 μM, Ca2+ channels conduct Na+. Due to the high affinity of the intrapore binding sites for Ca2+ relative to Na+, addition of μM concentrations of Ca2+ block Na+ conductance through the channel. There is little information, however, about the potential for interaction between Na+ and Ca2+ for the second binding site in a Ca2+ channel already occupied by one Ca2+. The two simplest possibilities, (a) that Na+ and Ca2+ compete for the second binding site or (b) that full time occupancy by one Ca2+ excludes Na+ from the pore altogether, would imply considerably different mechanisms of channel permeation. We are studying permeation mechanisms in N-type Ca2+ channels. Similar to L-type Ca2+ channels, N-type channels conduct Na+ well in the absence of external Ca2+. Addition of 10 μM Ca2+ inhibited Na+ conductance by 95%, and addition of 1 mM Mg2+ inhibited Na+ conductance by 80%. At divalent ion concentrations of 2 mM, 120 mM Na+ blocked both Ca2+ and Ba2+ currents. With 2 mM Ba2+, the IC50 for block of Ba2+ currents by Na+ was 119 mM. External Li+ also blocked Ba2+ currents in a concentration-dependent manner, with an IC50 of 97 mM. Na+ block of Ba2+ currents was dependent on [Ba2+]; increasing [Ba2+] progressively reduced block with an IC50 of 2 mM. External Na+ had no effect on voltage-dependent activation or inactivation of the channel. These data suggest that at physiological concentrations, Na+ and Ca2+ compete for occupancy in a pore already occupied by a single Ca2+. Occupancy of the pore by Na+ reduced Ca2+ channel conductance, such that in physiological solutions, Ca2+ channel currents are between 50 and 70% of maximal.
5
Kuo, Chung-Chin, and Bruce P. Bean. "G-protein modulation of ion permeation through N-type calcium channels." Nature 365, no. 6443 (September 1993): 258–62. http://dx.doi.org/10.1038/365258a0.
Full text
6
Doughty, Stephen W., Frank E. Blaney, and W. Graham Richards. "Models of ion pores in N-type voltage-gated calcium channels." Journal of Molecular Graphics 13, no. 6 (December 1995): 342–48. http://dx.doi.org/10.1016/0263-7855(95)00074-7.
Full text
7
Othman and Hamurtekin. "A New Pain Killer from the Nature: N-Type Calcium Channels Blockers." Proceedings 40, no. 1 (February 8, 2020): 47. http://dx.doi.org/10.3390/proceedings2019040047.
Full textAbstract:
N-type calcium channels (Neuronal-type Calcium channel, Cav2.2) is a member of high voltage activated calcium channels. There are two native small peptides for N-type calcium channels (NTCC) directly which are derived from cone snail, ω-conotoxin-GVIA isolated from Conus geographus and ω-conotoxin-MVIIA (SNX-111, Ziconotide, PrialtTM), from Conus magus which both directly block the α1-ion conducting pore. NTCCs, have been shown to play a key role in nociceptive transmission due to their strategic location, presynaptically in afferent C & Aᵹ fiber terminals and postsynaptically in descending neuron. NTCCs, which are highly expressed at the pre-synaptic terminals of nociceptive neurons in dorsal horn of the spinal cord regulate release of the key pro-nociceptive neurotransmitters such as glutamate, substance P, neurokinin A, and CGRP. There have been many preclinical studies demonstrating the effect of different NTCC blockers in various acute, inflammatory and neuropathic animal pain models. In 2004 ziconotide has been approved in US and Europe to be used in clinical practice. Furthermore, many clinical trials have been performed in more than 1000 patients studying the efficacy and safety of ziconotide. IT administrated of ziconotide showed significant decrease in pain scores in patients with malignant and nonmalignant pain which are practically in neuropathic pain characteristic and resistant to IT opioids.
8
Smith, Howard. "Hydrogen Sulfide’s Involvement in Modulating Nociception." September 2009 5;12, no. 5;9 (September 14, 2009): 901–10. http://dx.doi.org/10.36076/ppj.2009/12/901.
Full textAbstract:
Hydrogen sulfide (H2S) is a malodorous gas which functions as an endogenous gasotransmitter in humans. It is becoming appreciated that H2S may be involved in a wide variety of processes including nociceptive processes. The molecular mechanisms responsible for many of the activities of H2S remain uncertain, however, H2S increases cAMP levels in neuronal and glial cell lines and primary neuron cultures with hyperpolarization. H2S may be involved in multiple signaling pathways and produce various effects on ion channels (e.g. T-type calcium channel currents, ATP-sensitive K+ (KATP) channels) which may inhibit or promote nociception. It is also conceivable that H2S may affect the n-methyl-d aspartate (NMDA) receptor complex and/or TRPA1 ion channels which may modulate nociceptive processes. It appears that H2S may regulate key neuronal functions, including the induction of hippocampal long-term potentiation, a synaptic model of learning and memory thought to involve the NMDA receptor as well as the release of corticotrophinreleasing hormone from the hypothalamus. It seems that the primary role of H2S in nociceptive processes is the activation of T-type calcium channels leading to facilitation of pronociceptive processes. A secondary contribution to the facilitation of pronociceptive processes may come from H2S-induced activation. It would appear that much like other gasotransmitters (e.g. nitric oxide), endogenous H2S may be involved in multiple physiologic processes and its effects remain complex, difficult to predict, and may vary depending on the specific environment/circumstances/location where it is generated. A greater understanding of the clinically significant human physiology of H2S and hydrogen sulfide’s effects on modulating nociceptive processes may potentially lead to novel targets for improving analgesia. Key words: Pain, nociception, hydrogen sulfide, calcium channels, analgesia, potassium channels
9
Ebersbacher, Charles, Ameet Chimote, Silvana Obici, and Laura Conforti. "Leptin upregulates CRAC channel expression in T lymphocytes (IRC2P.444)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 58.1. http://dx.doi.org/10.4049/jimmunol.192.supp.58.1.
Full textAbstract:
Abstract Obesity is a major health problem associated with systemic diseases whose pathogenesis has been linked to inflammation, but the underlying mechanisms are poorly understood. Leptin, an adipokine secreted by adipose tissue, is known to augment the antigen-dependent release of pro-inflammatory cytokines by T lymphocytes. Cytokine production is tightly regulated by cytoplasmic Ca2+ (Cac ) which is under the control of ion channels (Kv1.3, KCa3.1, calcium release activated Ca2+channel [CRAC, formed by Orai1 and Stim1]). We tested the hypothesis that ion channels contribute to the pro-inflammatory effects of leptin. CD3+ T cells isolated from healthy human donors were treated with 100-250 ng/ml leptin and ion channels’ gene expression was measured by RT-qPCR. Leptin induced a dose- and time-dependent increase in Orai1 expression up to 1.53 ± 0.21 (100 ng/ml) and 2.04 ± 0.40 folds (250 ng/ml, n=3) at 12 h. There was no significant difference in Stim1, Kv1.3 and KCa3.1 expression. CRAC channels are important for activation-mediated Ca2+ influx in T cells. Thus, we investigated whether Orai1 regulation by leptin affects Cac using a protocol that bypasses the T cell receptor and allows assessment of ion channel-dependent changes in Cac. Incubation with leptin-depleted serum reduced Ca2+ fluxes, while addition of 250 ng/ml of leptin to the leptin-free serum augmented Ca2+ fluxes. These findings suggest that leptin may promote hyperactivity of T cells via upregulation of ion channels.
10
Kerschbaum, Hubert H., and Michael D. Cahalan. "Monovalent Permeability, Rectification, and Ionic Block of Store-operated Calcium Channels in Jurkat T Lymphocytes." Journal of General Physiology 111, no. 4 (April 1, 1998): 521–37. http://dx.doi.org/10.1085/jgp.111.4.521.
Full textAbstract:
We used whole-cell recording to characterize ion permeation, rectification, and block of monovalent current through calcium release-activated calcium (CRAC) channels in Jurkat T lymphocytes. Under physiological conditions, CRAC channels exhibit a high degree of selectivity for Ca2+, but can be induced to carry a slowly declining Na+ current when external divalent ions are reduced to micromolar levels. Using a series of organic cations as probes of varying size, we measured reversal potentials and calculated permeability ratios relative to Na+, PX/PNa, in order to estimate the diameter of the conducting pore. Ammonium (NH4+) exhibited the highest relative permeability (PNH4/PNa = 1.37). The largest permeant ion, tetramethylammonium with a diameter of 0.55 nm, had PTMA/PNa of 0.09. N-methyl-d-glucamine (0.50 × 0.64 × 1.20 nm) was not measurably permeant. In addition to carrying monovalent current, NH4+ reduced the slow decline of monovalent current (“inactivation”) upon lowering [Ca2+]o. This kinetic effect of extracellular NH4+ can be accounted for by an increase in intracellular pH (pHi), since raising intracellular pH above 8 reduced the extent of inactivation. In addition, decreasing pHi reduced monovalent and divalent current amplitudes through CRAC channels with a pKa of 6.8. In several channel types, Mg2+ has been shown to produce rectification by a voltage-dependent block mechanism. Mg2+ removal from the pipette solution permitted large outward monovalent currents to flow through CRAC channels while also increasing the channel's relative Cs+ conductance and eliminating the inactivation of monovalent current. Boltzmann fits indicate that intracellular Mg2+ contributes to inward rectification by blocking in a voltage-dependent manner, with a zδ product of 1.88. Ca2+ block from the outside was also found to be voltage dependent with zδ of 1.62. These experiments indicate that the CRAC channel, like voltage-gated Ca2+ channels, achieves selectivity for Ca2+ by selective binding in a large pore with current–voltage characteristics shaped by internal Mg2+.
11
Estrada, Juan A., and Marc P. Kaufman. "µ-Opioid receptors inhibit the exercise pressor reflex by closing N-type calcium channels but not by opening GIRK channels in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 314, no. 5 (May 1, 2018): R693—R699. http://dx.doi.org/10.1152/ajpregu.00380.2017.
Full textAbstract:
µ-Opioid G protein-coupled receptors (MOR) interact with ion channels to decrease neuronal excitability. In humans, intrathecal administration of the MOR agonist fentanyl inhibits the exercise pressor reflex, an effect that can be attributed to either the opening of inward rectifying potassium channels (GIRK) or the closing of N-type calcium channels. The purpose of this study was to determine if the highly selective MOR agonist [d-Ala2, N-MePhe4,Gly-ol]-enkephalin (DAMGO) attenuates the exercise pressor reflex and which of these two channels are responsible for this effect. In decerebrate rats, we determined the effect of intrathecal injection of either tertiapin-LQ, which blocks the GIRK channel or ω-conotoxin-GVIA, which blocks the N-type calcium channel on the exercise pressor reflex, which was evoked by contracting the triceps surae muscles. Initially, we established that intrathecal injection of DAMGO inhibited the exercise pressor reflex relative to no intrathecal injection or intrathecal saline injection ( P < 0.001, n = 5). We then found that intrathecal injection of two doses of tertiapin-LQ (1 and 10 µg) had no effect on the exercise pressor reflex ( n = 6 and n = 7, respectively; P > 0.05). Importantly, neither dose of tertiapin-LQ prevented the DAMGO-induced inhibition of the exercise pressor reflex. Last, we found that intrathecal injection of ω-conotoxin-GVIA markedly attenuated the exercise pressor reflex ( P < 0.001, n = 7). The cardioaccelerator response to contraction did not appear to be effected in any of the experiments. We conclude that N-type voltage-gated calcium channel inhibition appears to be the mechanism by which MOR activation inhibits the exercise pressor reflex in decerebrate rats.
12
Thompson, Gregory W., Magda Horackova, and J. Andrew Armour. "Ion channel modifying agents influence the electrical activity generated by canine intrinsic cardiac neurons in situ." Canadian Journal of Physiology and Pharmacology 78, no. 4 (March 1, 2000): 293–300. http://dx.doi.org/10.1139/y99-138.
Full textAbstract:
This study was designed to establish whether agents known to modify neuronal ion channels influence the behavior of mammalian intrinsic cardiac neurons in situ and, if so, in a manner consistent with that found previously in vitro. The activity generated by right atrial neurons was recorded extracellularly in varying numbers of anesthetized dogs before and during continuous local arterial infusion of several neuronal ion channel modifying agents. Veratridine (7.5 µM), the specific modifier of Na+-selective channels, increased neuronal activity (95% above control) in 80% of dogs tested (n = 25). The membrane depolarizing agent potassium chloride (40 mM) reduced neuronal activity (43% below control) in 84% of dogs tested (n = 19). The inhibitor of voltage-sensitive K+ channels, tetraethylammonium (10 mM), decreased neuronal activity (42% below control) in 73% of dogs tested (n = 11). The nonspecific potassium channel inhibitor barium chloride (5 mM) excited neurons (47% above control) in 13 of 19 animals tested. Cadmium chloride (200 µM), which inhibits Ca2+-selective channels and Ca2+-dependent K+ channels, increased neuronal activity (65% above control) in 79% of dogs tested (n = 14). The specific L-type Ca2+ channel blocking agent nifedipine (5 µM) reduced neuronal activity (52% blow control in 72% of 11 dogs tested), as did the nonspecific inhibitor of L-type Ca2+ channels, nickel chloride (5 mM) (36% below control in 69% of 13 dogs tested). Each agent induced either excitatory or inhibitory responses, depending on the agent tested. It is concluded that specific ion channels (INa, ICaL, IKv, and IKCa) that have been associated with intrinsic cardiac neurons in vitro are involved in their capacity to generate action potentials in situ.Key words: calcium channels, intrinsic cardiac neuron, potassium channels, sodium channels.
13
Pokkula, Swapna, and Santh Rani Thakur. "Icariin ameliorates partial sciatic nerve ligation induced neuropathic pain in rats: an evidence of in silico and in vivo studies." Journal of Pharmacy and Pharmacology 73, no. 7 (April 3, 2021): 874–80. http://dx.doi.org/10.1093/jpp/rgab021.
Full textAbstract:
Abstract Objectives Neuropathic pain (NP) is a chronic inflammation of the sciatic nerve, associated with complex pathophysiological events like neuronal ectopic discharge with changes in neurotransmitters, growth factors, receptors/ion channels including N-methyl-d-aspartate receptors, Transient receptor cation channels, Voltage-gated calcium channels. All these events eventually lead to inflammation and apoptosis of the sciatic nerve in NP. Icariin (ICA), a natural flavonoid is well known for its anti-inflammatory potential. Hence, the present study is designed to evaluate its anti-inflammatory potential against neuropathic pain using in silico and in vivo studies. Methods In silico studies were conducted using targets of N-methyl-D-aspartate receptor subtype-2B (NR2B), The capsaicin receptor transient receptor cation channel subfamily-V member-1 (TRPV1), N-type voltage-gated calcium (CaV2.2) channels. In in vivo studies, after partial sciatic nerve ligation surgery to animals, received their respective treatment for 21 days, further TNF-α, IL-6, Bax (proapoptotic) and Bcl-2 (antiapoptotic) expressions were estimated. Key findings ICA decreased the expressions of TNF-α, IL-6, Bax and increased expression of Bcl-2. In silico studies revealed a good energy binding score towards NR2B, TRPV1 receptors and CaV2.2 ion Channel. Conclusions ICA could be a promising agent in alleviating neuropathic pain by inhibiting NR2B, TRPV1 receptors and Cav2.2 channels, which induces anti-apoptotic potential and inhibits inflammation.
14
Amaye, Isis, Thomas Heinbockel, Julia Woods, Zejun Wang, Miguel Martin-Caraballo, and Patrice Jackson-Ayotunde. "6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity." International Journal of Environmental Research and Public Health 15, no. 8 (August 20, 2018): 1784. http://dx.doi.org/10.3390/ijerph15081784.
Full textAbstract:
A small library of novel fluorinated N-benzamide enaminones were synthesized and evaluated in a battery of acute preclinical seizure models. Three compounds (GSA 62, TTA 35, and WWB 67) were found to have good anticonvulsant activity in the 6-Hz ‘psychomotor’ 44-mA rodent model. The focus of this study was to elucidate the active analogs’ mode of action on seizure-related molecular targets. Electrophysiology studies were employed to evaluate the compounds’ ability to inhibit neuronal activity in central olfactory neurons, mitral cells, and sensory-like ND7/23 cells, which express an assortment of voltage and ligand-gated ion channels. We did not find any significant effects of the three compounds on action potential generation in mitral cells. The treatment of ND7/23 cells with 50 µM of GSA 62, TTA 35, and WWB 67 generated a significant reduction in the amplitude of whole-cell sodium currents. Similar treatment of ND7/23 cells with these compounds had no effect on T-type calcium currents, indicating that fluorinated N-benzamide enaminone analogs may have a selective effect on voltage-gated sodium channels, but not calcium channels.
15
Evans, J. Grayson, and Slobodan M. Todorovic. "Redox and trace metal regulation of ion channels in the pain pathway." Biochemical Journal 470, no. 3 (September 4, 2015): 275–80. http://dx.doi.org/10.1042/bj20150522.
Full textAbstract:
Given the clinical significance of pain disorders and the relative ineffectiveness of current therapeutics, it is important to identify alternative means of modulating nociception. The most obvious pharmacological targets are the ion channels that facilitate nervous transmission from pain sensors in the periphery to the processing regions within the brain and spinal cord. In order to design effective pharmacological tools for this purpose, however, it is first necessary to understand how these channels are regulated. A growing area of research involves the investigation of the role that trace metals and endogenous redox agents play in modulating the activity of a diverse group of ion channels within the pain pathway. In the present review, the most recent literature concerning trace metal and redox regulation of T-type calcium channels, NMDA (N-methyl-D-aspartate) receptors, GABAA (γ-aminobutyric acid A) receptors and TRP (transient receptor potential) channels are described to gain a comprehensive understanding of the current state of the field as well as to provide a basis for future thought and experimentation.
16
Vörös, Orsolya, György Panyi, and Péter Hajdu. "Molecular background of Orai1 accumulation in the immunological synapse." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 184.3. http://dx.doi.org/10.4049/jimmunol.202.supp.184.3.
Full textAbstract:
Abstract CRAC channels have a vital role in the activation of T lymphocytes, through their calcium influx. CRAC is composed of the ER-membrane resident STIM1 (stromal interaction molecule 1) and the plasma membrane Orai1 pore-forming subunit. Both are accumulated at the interface of the immunological synapse (IS) between a T cell and an antigen-presenting cell (APC). CRAC channelopathies due to mutations in either Orai1 or STIM1 are characterized by severe combined immunodeficiency (SCID)-like disease, autoimmunity, muscular hypotonia, and ectodermal dysplasia. The down-regulation of actin-binding protein expression (e.g. HS1), which may be responsible for the immobilization of ion channels, hampers Ca2+-signaling and IS formation of T lymphocytes. We hypothesized that actin-binding proteins modulate the trafficking of the CRAC channels to the IS, which is crucial for the Ca2+-signaling. By means of GST-affinity assay we could show that HS1, which is an actin-regulatory adaptor protein, binds to the N-terminus of the Orai1. N-terminal truncated Orai1 channels (ΔN1: 1–74, ΔN2: 1–88) were created and expressed in Jurkat cells. Then Orai1 channel expressing Jurkat cells were conjugated to CD3/CD28 beads as an APC and Orai1 polarization was determined: the Orai1-ΔN1 mutant similar to the wild-type Orai1 redistributed to the IS but the Orai1-ΔN2 did not. Furthermore, the HS1 protein did not show IS-accumulation in cells expressing the Orai1-ΔN2 subunits unlike for those transfected with the Orai1-ΔN1 or the wild-type constructs. Overall, these data indicate that Orai1-HS1 interaction could contribute to the anchoring of the Orai1 in the IS and can affect the Ca2+-signaling upon T cell activation.
17
Ferreira, Gonzalo, Jianxun Yi, Eduardo Ríos, and Roman Shirokov. "Ion-dependent Inactivation of Barium Current through L-type Calcium Channels." Journal of General Physiology 109, no. 4 (April 1, 1997): 449–61. http://dx.doi.org/10.1085/jgp.109.4.449.
Full textAbstract:
It is widely believed that Ba2+ currents carried through L-type Ca2+ channels inactivate by a voltage- dependent mechanism similar to that described for other voltage-dependent channels. Studying ionic and gating currents of rabbit cardiac Ca2+ channels expressed in different subunit combinations in tsA201 cells, we found a phase of Ba2+ current decay with characteristics of ion-dependent inactivation. Upon a long duration (20 s) depolarizing pulse, IBa decayed as the sum of two exponentials. The slow phase (τ ≈ 6 s, 21°C) was parallel to a reduction of gating charge mobile at positive voltages, which was determined in the same cells. The fast phase of current decay (τ ≈ 600 ms), involving about 50% of total decay, was not accompanied by decrease of gating currents. Its amplitude depended on voltage with a characteristic U-shape, reflecting reduction of inactivation at positive voltages. When Na+ was used as the charge carrier, decay of ionic current followed a single exponential, of rate similar to that of the slow decay of Ba2+ current. The reduction of Ba2+ current during a depolarizing pulse was not due to changes in the concentration gradients driving ion movement, because Ba2+ entry during the pulse did not change the reversal potential for Ba2+. A simple model of Ca2+-dependent inactivation (Shirokov, R., R. Levis, N. Shirokova, and E. Ríos. 1993. J. Gen. Physiol. 102:1005–1030) robustly accounts for fast Ba2+ current decay assuming the affinity of the inactivation site on the α1 subunit to be 100 times lower for Ba2+ than Ca2+.
18
Madias, Christopher, Ann C. Garlitski, John Kalin, and Mark S. Link. "L-Type Calcium Channels Do Not Play a Critical Role in Chest Blow Induced Ventricular Fibrillation: Commotio Cordis." Cardiology Research and Practice 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/5191683.
Full textAbstract:
Background. In a commotio cordis swine model, ventricular fibrillation (VF) can be induced by a ball blow to the chest believed secondary to activation of mechanosensitive ion channels. The purpose of the current study is to evaluate whether stretch induced activation of the L-type calcium channel may cause intracellular calcium overload and underlie the VF in commotio cordis.Method and Results. Anesthetized juvenile swine received 6 chest wall strikes with a 17.9 m/s lacrosse ball timed to the vulnerable period for VF induction. Animals were randomized to IV verapamil (n=6) or placebo (n=6). There was no difference in the observed frequency of VF between verapamil (19/26: 73%) and placebo (20/36: 56%) treated animals (p=0.16). There was also no significant difference in the combined endpoint of VF or nonsustained VF (21/26: 81% in verapamil versus 24/36: 67% in controls,p=0.22).Conclusions. In this experimental model of commotio cordis, verapamil did not prevent VF induction. Thus, in commotio cordis it is unlikely that stretch activation of the L-type calcium channel with resultant intracellular calcium overload plays a prominent role.
19
Murali, Swetha S., Ian A. Napier, Sarasa A. Mohammadi, Paul F. Alewood, Richard J. Lewis, and MacDonald J. Christie. "High-voltage-activated calcium current subtypes in mouse DRG neurons adapt in a subpopulation-specific manner after nerve injury." Journal of Neurophysiology 113, no. 5 (March 1, 2015): 1511–19. http://dx.doi.org/10.1152/jn.00608.2014.
Full textAbstract:
Changes in ion channel function and expression are characteristic of neuropathic pain. Voltage-gated calcium channels (VGCCs) are integral for neurotransmission and membrane excitability, but relatively little is known about changes in their expression after nerve injury. In this study, we investigate whether peripheral nerve ligation is followed by changes in the density and proportion of high-voltage-activated (HVA) VGCC current subtypes in dorsal root ganglion (DRG) neurons, the contribution of presynaptic N-type calcium channels in evoked excitatory postsynaptic currents (EPSCs) recorded from dorsal horn neurons in the spinal cord, and the changes in expression of mRNA encoding VGCC subunits in DRG neurons. Using C57BL/6 mice [8- to 11-wk-old males ( n = 91)] for partial sciatic nerve ligation or sham surgery, we performed whole cell patch-clamp recordings on isolated DRG neurons and dorsal horn neurons and measured the expression of all VGCC subunits with RT-PCR in DRG neurons. After nerve injury, the density of P/Q-type current was reduced overall in DRG neurons. There was an increase in the percentage of N-type and a decrease in that of P/Q-type current in medium- to large-diameter neurons. No changes were found in the contribution of presynaptic N-type calcium channels in evoked EPSCs recorded from dorsal horn neurons. The α2δ-1 subunit was upregulated by 1.7-fold and γ-3, γ-2, and β-4 subunits were all downregulated 1.7-fold in injured neurons compared with sham-operated neurons. This comprehensive characterization of HVA VGCC subtypes in mouse DRG neurons after nerve injury revealed changes in N- and P/Q-type current proportions only in medium- to large-diameter neurons.
20
MacLeish, Peter R., and Colin A. Nurse. "Ion Channel Compartments in Photoreceptors: Evidence From Salamander Rods With Intact and Ablated Terminals." Journal of Neurophysiology 98, no. 1 (July 2007): 86–95. http://dx.doi.org/10.1152/jn.00775.2006.
Full textAbstract:
Vertebrate photoreceptors are highly polarized sensory cells in which several different ionic currents have been characterized. In the present study we used whole cell voltage-clamp and optical imaging techniques, the former combined with microsurgical manipulations, and simultaneous recording of membrane current and intracellular calcium signals to investigate the spatial distribution of ion channels within isolated salamander rods. In recordings from intact rods with visible terminals, evidence for five previously identified ionic currents was obtained. These include two Ca2+-dependent, i.e., a Ca2+-dependent chloride current [ ICl(Ca)] and a large-conductance Ca2+- and voltage-dependent K+ or BK current [ IK(Ca)], and three voltage-dependent currents, i.e., a delayed-rectifier type current [ IK(V)], a hyperpolarization-activated cation current ( Ih), and a dihydropyridine-sensitive L-type calcium current ( ICa). Of these, ICl(Ca) was highly correlated with the presence of a terminal; rods with visible terminals expressed ICl(Ca) without exception ( n = 125), whereas approximately 71% of rods (40/56) without visible terminals lacked ICl(Ca). More significantly, ICl(Ca) was absent from all rods ( n = 33) that had their terminals ablated, and recordings from the same cell before and after terminal ablation led, in all cases ( n =10), to the loss of ICl(Ca). In contrast, IK(Ca), IK(V), and Ih remained largely intact after terminal ablation, suggesting that they arose principally from ion channels located in the soma and/or inner segment. The outward IK(Ca) in terminal-ablated rods was reversibly suppressed on “puffing” a Ca2+-free extracellular solution over the soma and was appreciably enhanced by the L-type Ca2+ channel agonist, Bay K 8644 (0.1–2 μM). These data indicate that rod photoreceptors possess discrete targeting mechanisms that preferentially sort ion channels mediating ICl(Ca) to the terminal.
21
Xiong, Qiu-Ju, Zhuang-Li Hu, Peng-Fei Wu, Lan Ni, Zhi-Fang Deng, Wen-Ning Wu, Jian-Guo Chen, and Fang Wang. "Acid-sensing ion channels contribute to the increase in vesicular release from SH-SY5Y cells stimulated by extracellular protons." American Journal of Physiology-Cell Physiology 303, no. 4 (August 15, 2012): C376—C384. http://dx.doi.org/10.1152/ajpcell.00067.2012.
Full textAbstract:
Acid-sensing ion channels (ASICs) have been reported to play a role in the neuronal dopamine pathway, but the exact role in neurotransmitter release remains elusive. Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line, which can release monoamine neurotransmitters. In this study, the expression of ASICs was identified in SH-SY5Y cells to further explore the role of ASICs in vesicular release stimulated by acid. We gathered evidence that ASICs could be detected in SH-SY5Y cells. In whole cell patch-clamp recording, a rapid decrease in extracellular pH evoked inward currents, which were reversibly inhibited by 100 μM amiloride. The currents were pH dependent, with a pH of half-maximal activation (pH0.5) of 6.01 ± 0.04. Furthermore, in calcium imaging and FM 1-43 dye labeling, it was shown that extracellular protons increased intracellular calcium levels and vesicular release in SH-SY5Y cells, which was attenuated by PcTx1 and amiloride. Interestingly, N-type calcium channel blockers inhibited the vesicular release induced by acidification. In conclusion, ASICs are functionally expressed in SH-SY5Y cells and involved in vesicular release stimulated by acidification. N-type calcium channels may be involved in the increase in vesicular release induced by acid. Our results provide a preliminary study on ASICs in SH-SY5Y cells and neurotransmitter release, which helps to further investigate the relationship between ASICs and dopaminergic neurons.
22
Cardoso, Fernanda C., Matthieu Schmit, Michael J. Kuiper, Richard J. Lewis, Kellie L. Tuck, and Peter J. Duggan. "Inhibition of N-type calcium ion channels by tricyclic antidepressants – experimental and theoretical justification for their use for neuropathic pain." RSC Medicinal Chemistry 13, no. 2 (2022): 183–95. http://dx.doi.org/10.1039/d1md00331c.
Full text
23
Makarenko, Vladislav V., Gias U. Ahmmed, Ying-Jie Peng, Shakil A. Khan, Jayasri Nanduri, Ganesh K. Kumar, Aaron P. Fox, and Nanduri R. Prabhakar. "CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia." Journal of Neurophysiology 115, no. 1 (January 1, 2016): 345–54. http://dx.doi.org/10.1152/jn.00775.2015.
Full textAbstract:
Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca2+]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca2+]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca2+]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)- N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca2+ channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca2+]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca2+ currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca2+ influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane.
24
De, Priyanka, Sreerupa Ghose Roy, Dipak Kar, and Arun Bandyopadhyay. "Excess of glucocorticoid induces myocardial remodeling and alteration of calcium signaling in cardiomyocytes." Journal of Endocrinology 209, no. 1 (January 31, 2011): 105–14. http://dx.doi.org/10.1530/joe-10-0431.
Full textAbstract:
Ventricular dysfunction is one of the important side effects of the anti-inflammatory agent, glucocorticoid (GC). The present study was undertaken to examine whether abnormal calcium signaling is responsible for cardiac dysfunction due to an excess of GC hormone. The synthetic GC drug, dexamethasone (DEX), significantly (P<0.001, n=20) increased heart weight to body weight ratio, left ventricular remodeling, and fibrosis. The microarray analysis showed altered expression of several genes encoding calcium cycling/ion channel proteins in DEX-treated rat heart. The altered expression of some of the genes was validated by real-time PCR and western blotting analyses. The expression of the L-type calcium channels and calsequestrin was increased, whereas sarcoendoplasmic reticulum calcium transport ATPase 2a (SERCA2a) and junctin mRNAs were significantly reduced in DEX-treated rat left ventricular tissues. In neonatal rat ventricular cardiomyocytes, DEX also increased the level of mRNAs of atrial- and brain natriuretic peptides, L-type calcium channels, and calsequestrin after 24 h of treatment, which were mostly restored by mifepristone. The caffeine-induced calcium release was prolonged by DEX compared to the sharp release in control cardiomyocytes. Taken together, these data show that impaired calcium kinetics may be responsible for cardiac malfunction by DEX. The results are important in understanding the pathophysiology of the heart in patients treated with excess GC.
25
Hsiao, Chie-Fang, Nanping Wu, and Scott H. Chandler. "Voltage-Dependent Calcium Currents in Trigeminal Motoneurons of Early Postnatal Rats: Modulation by 5-HT Receptors." Journal of Neurophysiology 94, no. 3 (September 2005): 2063–72. http://dx.doi.org/10.1152/jn.00178.2005.
Full textAbstract:
Trigeminal motoneurons relay the final output signals generated within the oral-motor pattern generating circuit(s) to muscles for execution of various motor patterns. In recent years, these motoneurons were shown to possess voltage dependent nonlinear membrane properties that allow them to actively participate in sculpting their final output. A complete understanding of the factors controlling trigeminal motoneuronal (TMN) discharge during oral-motor activity requires, at a minimum, a detailed understanding of the palette of ion channels responsible for membrane excitability and a determination of whether these ion channels are targets for modulation. Toward that end, we studied in detail the properties of calcium channels in TMNs and their susceptibility to modulation by 5-HT in rat brain slices. We found that based on pharmacological and voltage-dependent properties, high-voltage-activated (HVA) N-type [ω-conotoxin GVIA (ω-CgTX)]-sensitive, and to a lesser extent P/Q-type [ω-agatoxin IVA (ω-Aga IVA)]-sensitive, calcium channels make up the majority of the whole cell calcium current. 5-HT (5.0 μM) decreased HVA current by 31.3 ± 2.2%, and the majority of this suppression resulted from reduction of current flow through N- and P/Q-type calcium channels. In contrast, 5-HT had no effect on low-voltage-activated (LVA) current amplitude in TMNs. HVA calcium current inhibition was mimicked by 5-CT, a 5-HT1 receptor agonist, and by R(+)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), a specific 5-HT1A agonist. The effects of 5-HT were blocked by the 5-HT1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) but not by ketanserin, a 5-HT2/1C antagonist. Under current clamp, ω-CgTX and 5-HT were most effective in suppressing the mAHP and both increased the spike frequency and input/output gain in response to current injection. Calcium current modulation by 5-HT1A receptors likely is an important mechanism to fine tune the input/output gain of TMNs in response to small incoming synaptic inputs and accounts for some of the previously reported effects of 5-HT on TMN excitability during tonic and burst activity during oral-motor behavior.
26
Cox, D. H., and K. Dunlap. "Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence." Journal of General Physiology 104, no. 2 (August 1, 1994): 311–36. http://dx.doi.org/10.1085/jgp.104.2.311.
Full textAbstract:
We have studied the inactivation of high-voltage-activated (HVA), omega-conotoxin-sensitive, N-type Ca2+ current in embryonic chick dorsal root ganglion (DRG) neurons. Voltage steps from -80 to 0 mV produced inward Ca2+ currents that inactivated in a biphasic manner and were fit well with the sum of two exponentials (with time constants of approximately 100 ms and > 1 s). As reported previously, upon depolarization of the holding potential to -40 mV, N current amplitude was significantly reduced and the rapid phase of inactivation all but eliminated (Nowycky, M. C., A. P. Fox, and R. W. Tsien. 1985. Nature. 316:440-443; Fox, A. P., M. C. Nowycky, and R. W. Tsien. 1987a. Journal of Physiology. 394:149-172; Swandulla, D., and C. M. Armstrong. 1988. Journal of General Physiology. 92:197-218; Plummer, M. R., D. E. Logothetis, and P. Hess. 1989. Neuron. 2:1453-1463; Regan, L. J., D. W. Sah, and B. P. Bean. 1991. Neuron. 6:269-280; Cox, D. H., and K. Dunlap. 1992. Journal of Neuroscience. 12:906-914). Such kinetic properties might be explained by a model in which N channels inactivate by both fast and slow voltage-dependent processes. Alternatively, kinetic models of Ca-dependent inactivation suggest that the biphasic kinetics and holding-potential-dependence of N current inactivation could be due to a combination of Ca-dependent and slow voltage-dependent inactivation mechanisms. To distinguish between these possibilities we have performed several experiments to test for the presence of Ca-dependent inactivation. Three lines of evidence suggest that N channels inactivate in a Ca-dependent manner. (a) The total extent of inactivation increased 50%, and the ratio of rapid to slow inactivation increased approximately twofold when the concentration of the Ca2+ buffer, EGTA, in the patch pipette was reduced from 10 to 0.1 mM. (b) With low intracellular EGTA concentrations (0.1 mM), the ratio of rapid to slow inactivation was additionally increased when the extracellular Ca2+ concentration was raised from 0.5 to 5 mM. (c) Substituting Na+ for Ca2+ as the permeant ion eliminated the rapid phase of inactivation. Other results do not support the notion of current-dependent inactivation, however. Although high intracellular EGTA (10 mM) or BAPTA (5 mM) concentrations suppressed the rapid phase inactivation, they did not eliminate it. Increasing the extracellular Ca2+ from 0.5 to 5 mM had little effect on this residual fast inactivation, indicating that it is not appreciably sensitive to Ca2+ influx under these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
27
Cox, R. H., D. Katzka, and M. Morad. "Characteristics of calcium currents in rabbit portal vein myocytes." American Journal of Physiology-Heart and Circulatory Physiology 263, no. 2 (August 1, 1992): H453—H463. http://dx.doi.org/10.1152/ajpheart.1992.263.2.h453.
Full textAbstract:
The properties of voltage-dependent Ca2+ channels were studied in isolated portal vein myocytes using the whole cell voltage-clamp method. Ca2+ currents (ICa) were identified based on their activation and inactivation potential, their dependence on external Ca2+ ([Ca2+]o), their suppression by organic or inorganic Ca2+ channel blockers, their augmentation by BAY K 8644, and their insensitivity to tetrodotoxin or alterations in external Na+ ([Na+]o). Changing the holding potential from -90 to -40 mV decreased ICa from 4.6 +/- 0.6 to 2.0 +/- 0.3 pA/pF at 0 mV but did not shift its voltage dependence significantly. The voltage dependence of steady-state inactivation and activation was represented by Boltzmann distributions with the following parameters: inactivation, half-maximal voltage (V0.5) = -32 +/- 7 mV and slope factor (k) = 6.1 +/- 0.2 mV; activation, V0.5 = -15 +/- 4 mV and k = 5.6 +/- 0.6 mV. Doubling the [Ca2+]o increased ICa and shifted the voltage dependence of its activation and inactivation by approximately 10 mV toward more positive potentials without altering the window currents. Substituting Na+, Ba2+, or Sr2+ for Ca2+ as the charge carrier through the Ca2+ channel slowed the rate of its inactivation and shifted its voltage dependence toward more negative potentials. Divalent selectivity of the Ca2+ channel showed an apparent concentration dependence: at 2 mMISr less than IBa = ICa, while at 10 mM ICa less than ISr = IBa. Because 50-100 microM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abolished the apparent concentration dependence of the divalent ion selectivity, this phenomenon was attributed to a high Ca2+ selectivity of the channel. Our data support the presence of only one type of Ca2+ channel in rabbit portal vein myocytes with characteristics similar to the L-type Ca2+ channel described in other cells, but with somewhat different divalent selectivity, holding potential, and [Na+]o dependence.
28
Yanardag, Sirma, and Murat Ayaz. "SAH-Induced Electrophysiological Changes of Ventricular Myocytes and Role of N-acetylcysteine Protection." Journal of Neurological Surgery Part A: Central European Neurosurgery 80, no. 02 (October 31, 2018): 072–80. http://dx.doi.org/10.1055/s-0038-1655739.
Full textAbstract:
Background Electrocardiogram (ECG) changes in patients with subarachnoid hemorrhage (SAH) are frequent. ST- and/or T-wave changes in ECG seem to predominate. Study Aims To investigate the ion channel mechanisms of SAH-induced ventricular excitation-contraction coupling changes and the possible protective effect of N-acetylcysteine (NAC). Methods Three groups of rabbits were used for the experiments. In two groups, SAH was induced by replacing the cerebrospinal fluid (CSF) with fresh autologous blood. In the control group, CSF was replaced with isotonic saline. In one SAH group, NAC was administered daily beginning at SAH induction. On day 5, ventricular action potentials, ionic currents, contractions, and intracellular free ion concentrations were recorded from the myocytes. Results In the SAH group, no change was found in the sodium currents, but the transient outward potassium currents were depressed, rapid repolarizing currents were increased, and t-type calcium currents were increased. Contractions and the intracellular free calcium concentration were depressed. NAC treatment, in contrast, not only restores these electrical remodeling changes but also the contractile abnormalities in the cardiac myocytes. Conclusion The changes in the action potential duration can be attributed to the measured ionic current changes. However, the exact mechanism, other than the oxidative stress, by which the NAC treatment protects the cardiac muscle needs additional investigations.
29
Chambers, Jordan D., Joel C. Bornstein, Rachel M. Gwynne, Katerina Koussoulas, and Evan A. Thomas. "A detailed, conductance-based computer model of intrinsic sensory neurons of the gastrointestinal tract." American Journal of Physiology-Gastrointestinal and Liver Physiology 307, no. 5 (September 1, 2014): G517—G532. http://dx.doi.org/10.1152/ajpgi.00228.2013.
Full textAbstract:
Intrinsic sensory neurons (ISNs) of the enteric nervous system respond to stimuli such as muscle tension, muscle length, distortion of the mucosa, and the chemical content in the lumen. ISNs form recurrent networks that probably drive many intestinal motor patterns and reflexes. ISNs express a large number of voltage- and calcium-gated ion channels, some of which are modified by inflammation or repeated physiological stimuli, but how interactions between different ionic currents in ISNs produce both normal and pathological behaviors in the intestine remains unclear. We constructed a model of ISNs including voltage-gated sodium and potassium channels, N-type calcium channels, big conductance calcium-dependent potassium (BK) channels, calcium-dependent nonspecific cation channels (NSCa), intermediate conductance calcium-dependent potassium (IK) channels, hyperpolarization-activated cation ( Ih) channels, and internal calcium dynamics. The model was based on data from the literature and our electrophysiological studies. The model reproduced responses to short or long depolarizing current pulses and responses to long hyperpolarizing current pulses. Sensitivity analysis showed that Ih, IK, NSCa, and BK have the largest influence on the number of action potentials observed during prolonged depolarizations. The model also predicts that changes to the voltage of activation for Ih have a large influence on excitability, but changes to the time constant of activation for Ih have a minor effect. Our model identifies how interactions between different iconic currents influence the excitability of ISNs and highlights an important role for Ih in enteric neuroplasticity resulting from disease.
30
Large, R. J., M. A. Hollywood, G. P. Sergeant, K. D. Thornbury, S. Bourke, J. R. Levick, and N. G. McHale. "Ionic currents in intimal cultured synoviocytes from the rabbit." American Journal of Physiology-Cell Physiology 299, no. 5 (November 2010): C1180—C1194. http://dx.doi.org/10.1152/ajpcell.00028.2010.
Full textAbstract:
Hyaluronan, a joint lubricant and regulator of synovial fluid content, is secreted by fibroblast-like synoviocytes lining the joint cavity, and secretion is greatly stimulated by Ca2+-dependent protein kinase C. This study aimed to define synoviocyte membrane currents and channels that may influence synoviocyte Ca2+ dynamics. Resting membrane potential ranged from −30 mV to −66 mV (mean −45 ± 8.60 mV, n = 40). Input resistance ranged from 0.54 GΩ to 2.6 GΩ (mean 1.28 ± 0.57 GΩ; ν = 33). Cell capacitance averaged 97.97 ± 5.93 pF. Voltage clamp using Cs+ pipette solution yielded a transient inward current that disappeared in Ca2+-free solutions and was blocked by 1 μM nifedipine, indicating an L-type calcium current. The current was increased fourfold by the calcium channel activator FPL 64176 (300 nM). Using K+ pipette solution, depolarizing steps positive to −40 mV evoked an outward current that showed kinetics and voltage dependence of activation and inactivation typical of the delayed rectifier potassium current. This was blocked by the nonspecific delayed rectifier blocker 4-aminopyridine. The synoviocytes expressed mRNA for four Kv1 subtypes (Kv1.1, Kv1.4, Kv1.5, and Kv1.6). Correolide (1 μM), margatoxin (100 nM), and α-dendrotoxin block these Kv1 subtypes, and all of these drugs significantly reduced synoviocyte outward current. The current was blocked most effectively by 50 nM κ-dendrotoxin, which is specific for channels containing a Kv1.1 subunit, indicating that Kv1.1 is critical, either as a homomultimeric channel or as a component of a heteromultimeric Kv1 channel. When 50 nM κ-dendrotoxin was added to current-clamped synoviocytes, the cells depolarized by >20 mV and this was accompanied by an increase in intracellular calcium concentration. Similarly, depolarization of the cells with high external potassium solution caused an increase in intracellular calcium, and this effect was greatly reduced by 1 μM nifedipine. In conclusion, fibroblast-like synoviocytes cultured from the inner synovium of the rabbit exhibit voltage-dependent inward and outward currents, including Ca2+ currents. They thus express ion channels regulating membrane Ca2+ permeability and electrochemical gradient. Since Ca2+-dependent kinases are major regulators of synovial hyaluronan secretion, the synoviocyte ion channels are likely to be important in the regulation of hyaluronan secretion.
31
Cibulsky, Susan M., Hong Fei, and Irwin B. Levitan. "Syntaxin-1A Binds to and Modulates the Slo Calcium-Activated Potassium Channel via an Interaction That Excludes Syntaxin Binding to Calcium Channels." Journal of Neurophysiology 93, no. 3 (March 2005): 1393–405. http://dx.doi.org/10.1152/jn.00789.2004.
Full textAbstract:
From its position in presynaptic nerve terminals, the large conductance Ca2+-activated K+ channel, Slo, regulates neurotransmitter release. Several other ion channels known to control neurotransmitter release have been implicated in physical interactions with the neurotransmitter release machinery. For example, the Cav2.2 (N-type) Ca2+ channel binds to and is modulated by syntaxin-1A and SNAP-25. Furthermore, a close juxtaposition of Slo and Cav2.2 is presumed to be necessary for functional coupling between the two channels, which has been shown in neurons. We report that Slo exhibits a strong association with syntaxin-1A. Robust co-immunoprecipitation of Slo and syntaxin-1A occurs from transfected HEK293 cells as well as from brain. However, despite this strong interaction and the known association between syntaxin-1A and the II–III loop of Cav2.2, these three proteins do not co-immunoprecipitate in a trimeric complex from transfected HEK293 cells. The Slo-syntaxin-1A co-immunoprecipitation is not significantly influenced by [Ca2+]. Multiple relatively weak interactions may sum up to a tight physical coupling of full-length Slo with syntaxin-1A: the C-terminal tail and the S0–S1 loop of Slo each co-immunoprecipitate with syntaxin-1A. The presence of syntaxin-1A leads to reduced Slo channel activity due to an increased V1/2 for activation in 100 nM, 1 μM, and 10 μM Ca2+, reduced voltage-sensitivity in 1 μM Ca2+, and slower rates of activation in 10 μM Ca2+. Potential physiological consequences of the interaction between Slo and syntaxin-1A include enhanced excitability through modulation of Slo channel activity and reduced neurotransmitter release due to disruption of syntaxin-1A binding to the Cav2.2 II–III loop.
32
Cozzoli, Anna, Antonella Liantonio, Elena Conte, Maria Cannone, Ada Maria Massari, Arcangela Giustino, Antonia Scaramuzzi, et al. "Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase." American Journal of Physiology-Cell Physiology 307, no. 7 (October 1, 2014): C634—C647. http://dx.doi.org/10.1152/ajpcell.00372.2013.
Full textAbstract:
Angiotensin II (ANG II) plays a role in muscle wasting and remodeling; however, little evidence shows its direct effects on specific muscle functions. We presently investigated the acute in vitro effects of ANG II on resting ionic conductance and calcium homeostasis of mouse extensor digitorum longus (EDL) muscle fibers, based on previous findings that in vivo inhibition of ANG II counteracts the impairment of macroscopic ClC-1 chloride channel conductance (gCl) in the mdx mouse model of muscular dystrophy. By means of intracellular microelectrode recordings we found that ANG II reduced gCl in the nanomolar range and in a concentration-dependent manner (EC50 = 0.06 μM) meanwhile increasing potassium conductance (gK). Both effects were inhibited by the ANG II receptors type 1 (AT1)-receptor antagonist losartan and the protein kinase C inhibitor chelerythrine; no antagonism was observed with the AT2 antagonist PD123,319. The scavenger of reactive oxygen species (ROS) N-acetyl cysteine and the NADPH-oxidase (NOX) inhibitor apocynin also antagonized ANG II effects on resting ionic conductances; the ANG II-dependent gK increase was blocked by iberiotoxin, an inhibitor of calcium-activated potassium channels. ANG II also lowered the threshold for myofiber and muscle contraction. Both ANG II and the AT1 agonist L162,313 increased the intracellular calcium transients, measured by fura-2, with a two-step pattern. These latter effects were not observed in the presence of losartan and of the phospholipase C inhibitor U73122 and the in absence of extracellular calcium, disclosing a Gq-mediated calcium entry mechanism. The data show for the first time that the AT1-mediated ANG II pathway, also involving NOX and ROS, directly modulates ion channels and calcium homeostasis in adult myofibers.
33
Rodríguez, Yadira Ramírez, Karina Robledo Márquez, Ricardo Espinosa Tanguma, Alejandra Medina Hernández, Aldo Rodríguez Menchaca, Victoria Ramírez, Francisco Bautista Redonda, Lina Riego Ruiz, and Joyce Trujillo. "Vasoactive Effect Associated With Calcium Channel Blockade Through a Pitaya Juice Concentrate (Stenocereus Huastecorum): Identification of Bioactive Compounds." Current Developments in Nutrition 6, Supplement_1 (June 2022): 330. http://dx.doi.org/10.1093/cdn/nzac053.071.
Full textAbstract:
Abstract Objectives The aim is to evaluate the vasodilator effect of pitaya juice concentrate (PJC) in isolated rat aortic rings and to identify the responsible vasoactive compounds, as well as their mechanism of action. Methods The juice was obtained from S. huastecorum fruit. First, the fruit juice was centrifuged to obtain 1200 mL of PJC, 600 mL were frozen until use and 600 mL were lyophilized (LyPJC). LyPJC was fractionated by reverse phase chromatography. he profiling of the LyPJC was analyzed by HPLC-PAD and nuclear magnetic resonance (NMR). The vasoactive effect of PJC was evaluated in rings with (n = 5) and without endothelium (n = 5), pre-contracted with 10 mM phenylephrine (Phe). Next, 40 mg/mL of LyPJC was added, during 30 min. In separate experiments, the effect of 20 mM of tetraethylammonium ion (TEA, potassium channel blocker), or 200 nM of nifedipine (Nph, calcium channel blocker) was tested. Furthermore, the LyPJC fractions were evaluated in thoracic aorta rings and by patch clamp technique. Results The profiling of LyPJC by HPLC-PAD showed 16 types of betalains and 31 types of phenolic compounds. The NRM showed a type of betalain as the main compound of PJC. The LyPJC administration exhibited 4-fold greater vasodilation effect versus physiological solution (54.3% ± 14.1 vs 6.7% ± 3.7), endothelium independent. The TEA did not modify the vasodilator effect of LyPJC in rings. However, with Nph, the vasodilator effect was blocked. Finally, the 8 fractions obtained from LyPJC were evaluated in rings, only the first fraction (H2O: HOAc 1% without methanol) showed a vasodilatory effect. Patch clamp experiments showed that the LyPJC first fraction relaxing effect may be the result of its inhibitory effect on L-type calcium channels. Conclusions PJC contains betalains and phenolic compounds, with a vasodilatory effect associated with calcium channel blockade in isolated rat aortic rings. The first fraction will be purified and analyzed by mass spectrometry and the exact compound will be determined. Funding Sources Consejo Nacional de Ciencia y Tecnología (CONACYT- FORDECYT 296,354)-Instituto Potosino de Investigación Científica y Tecnológica A.C. (IPICYT).
34
Geiling, H., and D. Schild. "Glutamate-mediated release of Ca2+ in mitral cells of the olfactory bulb." Journal of Neurophysiology 76, no. 1 (July 1, 1996): 563–70. http://dx.doi.org/10.1152/jn.1996.76.1.563.
Full textAbstract:
1. Effects of glutamate on intracellular Ca2+ concentration ([Ca2+]i) were investigated in cultured olfactory bulb neurons of Xenopus laevis tadpoles. We imaged [Ca2+]i in these cells with the use of a confocal laser scanning microscope and the calcium indicator dyes Fluo3 and FuraRed. 2. In the standard bath solution, application of glutamate through a pipette resulted in an increase of [Ca2+]i in both mitral/ tufted (M/T) cells and interneurons. The increase occurred in all compartments of the cells, although in a nonhomogenous way. 3. In an ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-buffered bath solution (Ca(2+)-free Ringer solution), glutamate reproducibly induced an increase of [Ca2+]i in M/T cells but not in interneurons. This increase in [Ca2+]i had the following properties: 1) it was delayed with respect to the combined ionotropic and metabotropic response to glutamate, 2) in some cases it stopped before the end of the glutamate application, and 3) it was not affected by D,L-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione added to the bath. It was interpreted as a release of Ca2+ from intracellular calcium stores. 4. Of 47 M/T cells that showed a glutamate-mediated release of [Ca2+]i, 46 also showed Ca2+ influx through ionotropic glutamate receptors, so that intracellular release of [Ca2+]i appeared to be associated with the presence of glutamate-gated ion channels. However, of 110 M/T cells showing an ionotropic response to glutamate, only 46 showed a glutamate-mediated release of [Ca2+]i. 5. The glutamate-mediated release of [Ca2+]i in the dendrites was higher than that in the soma. No indications for calcium waves were found. 6. Quisqualate and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) mimicked the effect of glutamate on the release of [Ca2+]i, with potencies quisqualate > glutamate > > ACPD. N-acetyl-aspartyl-glutamate did not induce release of [Ca2+]i. The release was partly blocked by (+)-alpha-methyl-4-carboxyphenylglycine. 7. In conclusion, some but not all M/T cells of the olfactory bulb of X. laevis show a glutamate-mediated and predominantly dendritic increase of [Ca2+]i that is associated with glutamategated channels. The pharmacological properties of the corresponding metabotropic glutamate receptor (mGluR) resemble those of the mGluR1/5 receptors in rat.
35
Wright, Malcolm, Paresh Jobanputra, Charles Bavington, Donald M. Salter, and George Nuki. "Effects of Intermittent Pressure-Induced Strain on the Electrophysiology of Cultured Human Chondrocytes: Evidence for the Presence of Stretch-Activated Membrane Ion Channels." Clinical Science 90, no. 1 (January 1, 1996): 61–71. http://dx.doi.org/10.1042/cs0900061.
Full textAbstract:
1. Cyclical pressurization of cultured chondrocytes results in increases in cyclic AMP and in the rate of proteoglycan synthesis. Intermittent increases in hydrostatic pressure are also associated with hyperpolarization of chondrocyte cell membranes and activation of Ca2+-dependent K+-ion channels but the physiological basis for this response to mechanical stimulation is unclear. 2. Experiments have been undertaken to better define the types of ion channels involved and to explore the possibility that the hyperpolarization response associated with cyclical pressurization of chondrocytes follows activation of stretch-activated ion channels. 3. The mean membrane potential of chondrocytes in non-confluent monolayer cell culture rose from −15.3 ± 0.24 mV to −21.1 ± 0.28 mV (n = 60, P < 0.0001) after intermittent pressurization (0.33 Hz, 16 kPa, 20 min). 4. Strain gauge measurements showed that cyclical pressurization was associated with strain on the base of the culture plate. The amplitude of the hyperpolarization response was proportional to the microstrain to which cells were subjected. 5. Membrane hyperpolarization did not occur when chondrocytes were subjected to cyclical pressurization in rigid glass culture dishes or plastic dishes positioned in the pressurization chamber so as to avoid bending of the base of the culture dish. 6. Indirect evidence that the hyperpolarization response after intermittent pressure-induced strain was associated with stimulation of stretch-activated ion channels was obtained from experiments with gadolinium, amiloride and hexamethylene amiloride, each of which abolished hyperpolarization. 7. Experiments with apamin, charybdotoxin and iberiotoxin showed that the Ca2+-activated K+ channels involved in the hyperpolarization response are apamin-sensitive, charybdotoxin- and iberiotoxin-resistant, low-conductance channels. 8. Somatostatin and cadmium chloride, which block L-type calcium channels, abolished strain-induced chondrocyte hyperpolarization. EGTA, which chelates extracellular Ca2+, reduced the response to 48% of control values, and thapsigargin, which raises intracellular Ca2+ by inhibition of Ca2+—ATPase in endoplasmic reticulum, caused hyperpolarization independently with further hyperpolarization after pressure-induced strain. These data indicate that chondrocyte hyperpolarization was dependent on intracellular Ca2+ concentrations. 9. Further work is required to determine whether stretch-activated ion channels shown to be associated with chondrocyte hyperpolarization after cyclical pressure-induced strain are also involved in the signal transduction process that leads to increases in proteoglycan synthesis.
36
Farrell, Spring R., Iona D. Raymond, Michael Foote, Nicholas C. Brecha, and Steven Barnes. "Modulation of Voltage-Gated Ion Channels in Rat Retinal Ganglion Cells Mediated by Somatostatin Receptor Subtype 4." Journal of Neurophysiology 104, no. 3 (September 2010): 1347–54. http://dx.doi.org/10.1152/jn.00098.2010.
Full textAbstract:
Somatostatin (somatotropin release-inhibiting factor [SRIF]) is known to modulate the excitability of retinal ganglion cells, but the membrane mechanisms responsible and the extent to which intracellular calcium signaling is affected have not been determined. We show that somatostatin receptor subtype 4 (sst4) is expressed specifically in rat ganglion cells and that the generation of repetitive action potentials by isolated ganglion cells is reduced in the presence of L-803,087, a selective sst4 agonist (10 nM). Under voltage clamp, L-803,087 increased outward K+ currents by 51.1 ± 13.1% at 0 mV and suppressed Ca2+ channel currents by 32.5 ± 9.4% at −10 mV in whole cell patch-clamped ganglion cells. The N-type Ca2+ channel blocker ω-conotoxin GVIA (CTX, 1 μM) reduced L-type Ca2+ current ( ICa) in ganglion cells by 43.5 ± 7.2% at −10 mV, after which addition of L-803,087 further reduced ICa by 28.0 ± 16.0% . In contrast, ganglion cells treated first with nifedipine (NIF, 10 μM), which blocked 46.1 ± 3.5% of the control current at −10 mV, did not undergo any further reduction in ICa in the presence of L-803,087 (−3.5 ± 3.8% vs. NIF), showing that stimulation of sst4 reduces Ca2+ influx through L-type Ca2+ channels. To assess the effects of sst4 stimulation on intracellular Ca2+ levels ([Ca2+]i) in ganglion cells, fura-2 was used to measure changes in [Ca2+]i in response to depolarization induced by elevated [K+]o. [Ca2+]i was increased to a lesser extent (86%) in the presence of L-803,087 compared with recordings made in the absence of the sst4 agonist and this effect was blocked by NIF (10 μM). Suppression of spiking and Ca2+ signaling via sst4 may contribute to the reported neuroprotective actions of somatostatin and promote ganglion cell survival following ischemia and axonal trauma.
37
Davis, S. F., and C. L. Linn. "Activation of NMDA receptors linked to modulation of voltage-gated ion channels and functional implications." American Journal of Physiology-Cell Physiology 284, no. 3 (March 1, 2003): C757—C768. http://dx.doi.org/10.1152/ajpcell.00252.2002.
Full textAbstract:
Catfish ( Ictalurus punctatus) cone horizontal cells contain N-methyl-d-aspartate (NMDA) receptors, the function of which has yet to be determined. In the present study, we have examined the effect of NMDA receptor activation on voltage-gated ion channel activity. NMDA receptor activation produced a long-term downregulation of voltage-gated sodium and calcium currents but had no effect on the delayed rectifying potassium current. NMDA's effect was eliminated in the presence of AP-7. To determine whether NMDA receptor activation had functional implications, isolated catfish cone horizontal cells were current clamped to mimic the cell's physiological response. When horizontal cells were depolarized, they elicited a single depolarizing overshoot and maintained a depolarized steady state membrane potential. NMDA reduced the amplitude of the depolarizing overshoot and increased the depolarized steady-state membrane potential. Both effects of NMDA were eliminated in the presence of AP-7. These results support the hypothesis that activation of NMDA receptors in catfish horizontal cells may affect the type of visual information conveyed through the distal retina.
38
Shingai, R., and B. N. Christensen. "Excitable properties and voltage-sensitive ion conductances of horizontal cells isolated from catfish (Ictalurus punctatus) retina." Journal of Neurophysiology 56, no. 1 (July 1, 1986): 32–49. http://dx.doi.org/10.1152/jn.1986.56.1.32.
Full textAbstract:
External horizontal cells were enzymatically dissociated from intact catfish (Ictalurus punctatus) retina and pipetted onto a small chamber attached to the stage of an inverted phase-contrast microscope. Individual horizontal cells were recognized by their large size and restricted dendritic arborization. Low-resistance (3-12 M omega) patch-type electrodes were used to record intracellular potentials and to pass current across the cell membrane under either current or voltage-clamp conditions. The average resting potential of isolated horizontal cells was -67 V + 6.9 mV (mean +/- SD, n = 40). At the resting potential, the cell membrane appears to be mainly permeable to K. A depolarizing current step evoked an action potential in the cell. The maximum rate of rise of the action potential (dV/dt) in normal physiological solution was 6.5 +/- 1.8 V/s (means +/- SD, n = 24) and was reduced to 1.2 +/- 0.39 V/s (means +/- SD, n = 9) in 1-10 micron tetrodotoxin (TTX) and 3.2 +/- 1.4 V/s (means +/- SD, n = 6) in Ca-free solution. The maximum dV/dt was reduced in 10 mM extracellular K concentration [K]o to about half of that seen in standard saline, and values in 30 or 80 mM [K]o were similar to that measured in TTX. Following an action potential, the membrane potential reached a plateau potential of + 17.4 +/- 8.1 mV (means +/- SD, n = 17) and remained depolarized for variable periods of time lasting from less than a second to a few minutes. When the plateau potential was long lasting, the cell repolarized slowly and upon reaching zero rapidly repolarized to the original resting potential. The duration of the plateau potential decreased or was absent in saline containing one of the following calcium channel antagonists: La, Cd, Co, or Ni. The voltage-clamp technique was used to identify the membrane currents responsible for the membrane potential changes seen under current clamp. Experiments were carried out using either a single or two individual electrodes. Fast and steady-state inward currents were recorded from isolated horizontal cells in the voltage range between -20 and +20 mV. These currents were a result of increased membrane conductance to both Na and Ca ions. The Na channels are inactivated at depolarized potentials and are TTX sensitive. Ca channels are partially inactivated at depolarized potentials. The Ca conductance is decreased by Cd, Co, Ni, and La. Ba can substitute for Ca in the channel.(ABSTRACT TRUNCATED AT 400 WORDS)
39
Long, Wen, Yu Zhao, Lubo Zhang, and Lawrence D. Longo. "Role of Ca2+ channels in NE-induced increase in [Ca2+]iand tension in fetal and adult cerebral arteries." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 277, no. 1 (July 1, 1999): R286—R294. http://dx.doi.org/10.1152/ajpregu.1999.277.1.r286.
Full textAbstract:
In vascular smooth muscle, elevation of agonist-induced intracellular Ca2+ concentration ([Ca2+]i) occurs via both Ca2+ release from intracellular stores and Ca2+influx across the plasma membrane. In the cerebral vasculature of the fetus and adult the relative roles of these mechanisms have not been defined. To test the hypothesis that plasma membrane L-type and receptor-operated Ca2+ channels play a key role in NE-induced vasoconstriction via alterations in plasma membrane Ca2+ flux and that this may change with developmental age, we performed the following study. In main branch middle cerebral arteries (MCA) from near-term fetal (∼140 days) and nonpregnant adult sheep, we quantified NE-induced responses of vascular tension and [Ca2+]i(by use of fura 2) under standard conditions in response to several Ca2+ channel blockers and in response to zero extracellular Ca2+. In fetal and adult MCA, maximal NE-induced tensions (g) were 0.91 ± 0.12 ( n = 10) and 1.61 ± 0.13 ( n = 12), respectively. The pD2 values for NE-induced tension were both 6.0 ± 0.1, whereas the fetal and adult maximum responses (%Kmax) were 107 ± 16 and 119 ± 7, respectively. The fetal and adult pD2 values for NE-induced increase of [Ca2+]iwere 6.2 ± 0.1 and 6.4 ± 0.1, respectively, whereas maximum [Ca2+]iresponses were 81 ± 9 and 103 ± 15% of Kmax, respectively. After 10−5 M NE-induced contraction, nifedipine resulted in dose-dependent decrease in vessel tone and [Ca2+]iwith pIC50 values for fetal and adult tensions of 7.3 ± 0.1 and 6.6 ± 0.1, respectively ( P < 0.01; n = 4 each), whereas pIC50 for [Ca2+]iresponses were 7.2 ± 0.1 and 6.9 ± 0.1, respectively. The pIC50 values for tension for diltiazem and verapamil were somewhat lower but showed a similar relationship. The receptor-operated Ca2+ channel blocker 2-nitro-4 carboxyphenyl- N,N-diphenyl carbamate showed little effect on NE-induced vessel contractility or [Ca2+]i. In the absence of extracellular Ca2+ for 2 min, 10−5 M NE resulted in markedly attenuated responses of adult MCA tension and [Ca2+]ito 39 ± 7 and 73 ± 8% of control values ( n = 4). For fetal MCA, exposure to extracellular Ca2+concentration resulted in essentially no contractile or [Ca2+]iresponse ( n = 4). Similar blunting of NE-induced tension and [Ca2+]iwas seen in response to 10−3M lanthanum ion. These findings provide evidence to suggest that especially in fetal, but also in adult, ovine MCA, Ca2+ flux via L-type calcium channels plays a key role in NE-induced contraction. In contrast, Ca2+ flux via receptor-operated Ca2+ channels is of less importance. This developmental difference in the role of cerebrovascular plasma membrane Ca2+ channels may be an important association with increased Ca2+sensitivity of the fetal vessels.
40
Berlin, J. R. "Spatiotemporal changes of Ca2+ during electrically evoked contractions in atrial and ventricular cells." American Journal of Physiology-Heart and Circulatory Physiology 269, no. 3 (September 1, 1995): H1165—H1170. http://dx.doi.org/10.1152/ajpheart.1995.269.3.h1165.
Full textAbstract:
Spatial and temporal changes of intracellular calcium ion concentration ([Ca2+]i) during stimulated contractions were observed by confocal microscopy in rat ventricular and guinea pig atrial myocytes. Fluorescence intensity profiles in fluo 3-acetoxymethyl ester (fluo 3-AM)-loaded cells were collected from the entire cell, selected regions of the cell, or along a single scanned line across the cell. In rat ventricular myocytes, the increase of [Ca2+]i after a single stimulus from field electrodes occurred synchronously across the cell whether fluo 3 fluorescence was monitored in a narrow region aligned with the long axis of the cell or in line-scan images of a single z-line across the cell. However, during the onset of Ca2+ channel blockade by nifedipine (5 microM), electrical stimulation produced spatially nonuniform, focal increases of [Ca2+]i. In guinea pig atrial myocytes, stimulated increases of [Ca2+]i first appeared in focal regions at the cell periphery before spreading to the cell interior. Line-scan images showed the peripheral rise of [Ca2+]i led that at the center of the cell by 34 +/- 4 ms (mean +/- SE, n = 3). These data demonstrate that the t-tubular network ensures synchronous increases of [Ca2+]i throughout the cell during an action potential. In the absence of t tubules or when the number of sarcolemmal Ca2+ channels opened by membrane depolarization is greatly reduced, stimulated increases of [Ca2+]i can be observed to arise in focal regions of the cell.
41
Stueber, Thomas, Mirjam J. Eberhardt, Christoph Hadamitzky, Annette Jangra, Stefan Schenk, Felicia Dick, Carsten Stoetzer, et al. "Quaternary Lidocaine Derivative QX-314 Activates and Permeates Human TRPV1 and TRPA1 to Produce Inhibition of Sodium Channels and Cytotoxicity." Anesthesiology 124, no. 5 (May 1, 2016): 1153–65. http://dx.doi.org/10.1097/aln.0000000000001050.
Full textAbstract:
Abstract Background The relatively membrane-impermeable lidocaine derivative QX-314 has been reported to permeate the ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1) to induce a selective inhibition of sensory neurons. This approach is effective in rodents, but it also seems to be associated with neurotoxicity. The authors examined whether the human isoforms of TRPV1 and TRPA1 allow intracellular entry of QX-314 to mediate sodium channel inhibition and cytotoxicity. Methods Human embryonic kidney 293 (HEK-293) cells expressing wild-type or mutant human (h) TRPV1 or TRPA1 constructs as well as the sodium channel Nav1.7 were investigated by means of patch clamp and ratiometric calcium imaging. Cytotoxicity was examined by flow cytometry. Results Activation of hTRPA1 by carvacrol and hTRPV1 by capsaicin produced a QX-314–independent reduction of sodium current amplitudes. However, permeation of QX-314 through hTRPV1 or hTRPA1 was evident by a concentration-dependent, use-dependent inhibition of Nav1.7 activated at 10 Hz. Five and 30 mM QX-314 activated hTRPV1 via mechanisms involving the intracellular vanilloid-binding domain and hTRPA1 via unknown mechanisms independent of intracellular cysteins. Expression of hTRPV1, but not hTRPA1, was associated with a QX-314–induced cytotoxicity (viable cells 48 ± 5% after 30 mM QX-314) that was ameliorated by the TRPV1 antagonist 4-(3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide (viable cells 81 ± 5%). Conclusions The study data demonstrate that QX-314 directly activates and permeates the human isoforms of TRPV1 and TRPA1 to induce inhibition of sodium channels, but also a TRPV1-dependent cytotoxicity. These results warrant further validation of this approach in more intact preparations and may be valuable for the development of this concept into clinical practice.
42
Meech, R. W., and G. O. Mackie. "Synaptic potentials and threshold currents underlying spike production in motor giant axons of Aglantha digitale." Journal of Neurophysiology 74, no. 4 (October 1, 1995): 1662–70. http://dx.doi.org/10.1152/jn.1995.74.4.1662.
Full textAbstract:
1. Motor giant axons that excite swimming muscles in the jelly-fish Aglantha digitale interface with units of the inner and outer nerve rings in the margin at the base of the bell. External recording electrodes were used to monitor electrical activity at different sites within the nerve ring while events in the motor giant axon were recorded with intracellular micropipettes placed within 100 microns of the synaptic area. In some experiments, 4- to 6-micron-diam patch pipettes were used to record in situ from ion channel clusters at different locations along the axon. 2. Independently propagating calcium and sodium spikes in the motor giant axon were found to arise from different excitatory postsynaptic potentials (EPSPs). Two separate inputs were identified; one EPSP class represented an input from the pacemaker system in the inner nerve ring, whereas another represented an input from the giant axon in the outer nerve ring. EPSPs from the two nerve rings had significantly different time courses and amplitudes. EPSPs from the ring giant axon reached a peak in little more than 1 ms, whereas EPSPs from the pacemaker system reached a maximum in approximately 7 ms. These slower EPSPs may be compound events composed of postsynaptic potentials from multiple synapses excited in series by the passage of the pacemaker neuron signal. 3. The threshold for the production of calcium spikes by the slow EPSPs of the pacemaker system (-51 +/- 2.2 mV, mean +/- SD; n = 5) corresponded well with the voltage at which a net inward “T”-type calcium current first appeared in recordings from axon membrane patches (-55 to -50 mV); the threshold for the initiation of the sodium spike by the fast EPSPs of the ring giant system (-32 +/- 1.2 mV, mean +/- SD; n = 6) corresponded well with the voltage at which a net inward sodium current first appeared (-35 to -30 mV). 4. Inward currents were rarely observed in membrane patches formed using pipettes with tips of < 1 micron OD. Even with 4-micron pipettes, patches of membrane were sometimes obtained with a channel population consisting exclusively of potassium channels; calcium and sodium currents were found in highly discrete areas (“hot spots”). Preliminary findings on the undersurface of the axon, which makes synaptic contact with the myoepithelium, are consistent with a similar distribution. 5. The pathway by which the ring giant excites the motor giant axon is not definitely known. The synaptic delay between the peak of the ring giant action potential (monitored externally) and the initial rise of the fast EPSP (1.64 +/- 0.15 ms, mean +/- SD; n = 21) would allow for transmission at two synapses, because single synaptic delays at neuromuscular junctions in Aglantha are approximately 0.7 ms at 12 degrees C. The mean synaptic delay at the slow EPSP synapse was 0.88 +/- 0.09 (SD) ms (n = 12). 6. The delay between the impulse in the ring giant axon and the subsequent excitation of the motor giant axon may permit the animal to withdraw its tentacles and so lower the drag that would otherwise reduce the effectiveness of any escape swim and might induce tentacle autotomy.
43
Qi, Mengwen, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, and Ling Chen. "Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons." Cellular Physiology and Biochemistry 45, no. 3 (2018): 1084–96. http://dx.doi.org/10.1159/000487350.
Full textAbstract:
Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly) and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET) increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047) and GlyR (strychnine), indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC) (BIM II or D-sphingosine) or calcium/calmodulin-dependent protein kinase II (CaMKII) (KN-62 or KN-93) antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv.) injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.
44
Hofman, Paul L., Kelly Hiatt, Mervin C. Yoder, and Scott A. Rivkees. "A1 adenosine receptors potently regulate heart rate in mammalian embryos." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 273, no. 4 (October 1, 1997): R1374—R1380. http://dx.doi.org/10.1152/ajpregu.1997.273.4.r1374.
Full textAbstract:
A1adenosine receptors (A1ARs) have been recently shown to be expressed in rodent embryonic hearts at very early stages of development. To determine the functional significance of fetal cardiac A1AR expression during embryogenesis, murine fetal heart preparations were studied between postconceptual days 9 and 12. Dose-response curves generated using a variety of adenosine agonists revealed that A1AR activation potently regulated fetal heart rates. The A1AR agonist, N 6-cyclopentyladenosine, inhibited heart rates in a dose-dependent manner (half-maximal effective concentration = 3.6 × 10−8 M) and stopped fetal cardiac contractions in 63% of preparations. In contrast, A2a and A2b receptor activation did not alter heart rates, and activation of A3 receptors produced modest declines in heart rates. Endogenous adenosine also acted tonically to suppress fetal heart rates, as demonstrated by the A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine, increasing heart rates, whereas the adenosine reuptake blocker dipyridamole lowered fetal heart rates. Pertussis toxin treatment blocked A1AR action, showing that A1AR action was G protein mediated. Using drugs that alter cAMP levels and ion channel action, we were able to show that A1AR action involves events mediated by cAMP, ATP-dependent K, L-type calcium, sodium, and chloride channels, and the pacemaker current. These data show that adenosine and A1ARs potently regulate mammalian heart rates via multiple effector systems at very early stages of prenatal development.
45
Schild, J. H., J. W. Clark, M. Hay, D. Mendelowitz, M. C. Andresen, and D. L. Kunze. "A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics." Journal of Neurophysiology 71, no. 6 (June 1, 1994): 2338–58. http://dx.doi.org/10.1152/jn.1994.71.6.2338.
Full textAbstract:
1. Neurons of the nodose ganglia provide the sole connection between many types of visceral sensory inputs and the central nervous system. Electrophysiological studies of isolated nodose neurons provide a practical means of measuring individual cell membrane currents and assessing their putative contributions to the overall response properties of the neuron and its terminations. Here, we present a comprehensive mathematical model of an isolated nodose sensory neuron that is based upon numerical fits to quantitative voltage- and current-clamp data recorded in our laboratory. Model development was accomplished using an iterative process of electrophysiological recordings, nonlinear parameter estimation, and computer simulation. This work is part of an integrative effort aimed at identifying and characterizing the fundamental ionic mechanisms participating in the afferent neuronal limb of the baroreceptor reflex. 2. The neuronal model consists of two parts: a Hodgkin-Huxley-type membrane model coupled to a lumped fluid compartment model that describes Ca2+ ion concentration dynamics within the intracellular and external perineuronal media. Calcium buffering via a calmodulin-type buffer is provided within the intracellular compartment. 3. The complete model accurately reproduces whole-cell voltage-clamp recordings of the major ion channel currents observed in enzymatically dispersed nodose sensory neurons. Specifically, two Na+ currents exhibiting fast (INaf) and slow tetrodotoxin (TTX)-insensitive (INas) kinetics; low- and high-threshold Ca2+ currents exhibiting transient (ICa,t) and long-lasting (ICa,n) dynamics, respectively; and outward K+ currents consisting of a delayed-rectifier current (IK), a transient outward current (I(t)) and a Ca(2+)-activated K+ current (IK,Ca). 4. Whole-cell current-clamp recordings of somatic action-potential dynamics were performed on enzymatically dispersed nodose neurons using the perforated patch-clamp technique. Stimulus protocols consisted of both short (< or = 2.0 ms) and long (> or = 200 ms) duration current pulses over a wide range of membrane holding potentials. These studies clearly revealed two populations of nodose neurons, often termed A- and C-type cells, which exhibit markedly different action-potential signatures and stimulus response properties. 5. Using a single set of equations, the model accurately reproduces the electrical behavior of both A- and C-type nodose neurons in response to a wide variety of stimulus conditions and membrane holding potentials. The structure of the model, as well as the majority of its parameters are the same for both A- and C-type implementations.(ABSTRACT TRUNCATED AT 400 WORDS)
46
Sivaramakrishnan, S., M. S. Brodwick, and G. D. Bittner. "Presynaptic facilitation at the crayfish neuromuscular junction. Role of calcium-activated potassium conductance." Journal of General Physiology 98, no. 6 (December 1, 1991): 1181–96. http://dx.doi.org/10.1085/jgp.98.6.1181.
Full textAbstract:
Membrane potential was recorded intracellularly near presynaptic terminals of the excitor axon of the crayfish opener neuromuscular junction (NMJ), while transmitter release was recorded postsynaptically. This study focused on the effects of a presynaptic calcium-activated potassium conductance, gK(Ca), on the transmitter release evoked by single and paired depolarizing current pulses. Blocking gK(Ca) by adding tetraethylammonium ion (TEA; 5-20 mM) to a solution containing tetrodotoxin and aminopyridines caused the relation between presynaptic potential and transmitter release to steepen and shift to less depolarized potentials. When two depolarizing current pulses were applied at 20-ms intervals with gK(Ca) not blocked, the presynaptic voltage change to the second (test) pulse was inversely related to the amplitude of the first (conditioning) pulse. This effect of the conditioning prepulse on the response to the test pulse was eliminated by 20 mM TEA and by solutions containing 0 mM Ca2+/1 mM EGTA, suggesting that the reduction in the amplitude of the test pulse was due to activation of gK(Ca) by calcium remaining from the conditioning pulse. In the absence of TEA, facilitation of transmitter release evoked by a test pulse increased as the conditioning pulse grew from -40 to -20 mV, but then decreased with further increase in the conditioning depolarization. A similar nonmonotonic relationship between facilitation and the amplitude of the conditioning depolarization was reported in previous studies using extracellular recording, and interpreted as supporting an additional voltage-dependent step in the activation of transmitter release. We suggest that this result was due instead to activation of a gK(Ca) by the conditioning depolarization, since facilitation of transmitter release increased monotonically with the amplitude of the conditioning depolarization, and the early time course of the decay of facilitation was prolonged when gK(Ca) was blocked. The different time courses for decay of the presynaptic potential (20 ms) and facilitation (greater than 50 ms) suggest either that residual free calcium does not account for facilitation at the crayfish NMJ or that the transmitter release mechanism has a markedly higher affinity or stoichiometry for internal free calcium than does gK(Ca). Finally, our data suggest that the calcium channels responsible for transmitter release at the crayfish NMJ are not of the L, N, or T type.
47
Boni, R., N. Cocchia, F. Silvestre, G. Tortora, R. Lorizio, and E. Tosti. "279 PLASMA MEMBRANE ELECTRICAL PROPERTIES AND INTRACELLULAR CALCIUM STORES IN IMMATURE AND IN VITRO-MATURED ADULT AND JUVENILE SHEEP OOCYTES." Reproduction, Fertility and Development 17, no. 2 (2005): 290. http://dx.doi.org/10.1071/rdv17n2ab279.
Full textAbstract:
The low developmental efficiency recorded in juvenile oocytes represents, besides its technological relevance, an opportunity for increasing the knowledge of mechanisms regulating developmental competence in the oocytes. To analyze the biological reasons that make an adult oocyte different from a juvenile one, we monitored membrane electrical properties, i.e. resting potential, steady-state conductance and calcium currents, and calcium stores in these two oocyte types both at immature (GV) stage and after in vitro maturation (MII). Ovaries of cycling ewes and 40-day-old lambs were collected at abattoir and transported at 30°C. Cumulus-oocyte complexes (COC) were recovered by mincing. In vitro maturation was carried out in TCM199 supplemented with 10% fetal calf serum, 10 IU/mL of LH, 0.1 IU/mL of FSH, and 1 mg/mN of 17β-estradiol at 39.0°C in 5% CO2 for 24 h. Zona pellucida of immature and in vitro-matured oocytes was removed after incubation for 1–1.5 min in 0.5% (w/v) protease solution. Zona-free oocytes were placed in Ham F10 at 38.5°C and voltage clamped by standard techniques (Tosti et al. 2002 Reproduction 124, 835–846). After obtaining a giga-seal, the patch was ruptured. The permeability of the plasma membrane was verified by applying depolarizing and hyperpolarizing voltage steps of 10 mV and 500 ms before and at the peak current to generate the voltage-dependent currents. The voltage clamp was set at −80 and −30 mV to differentiate the Ca2+ current components, i.e. L-type Ca2+ channels. For intracellular calcium determinations, oocytes were placed in Ham F10 and injected with the 0.5 mM calcium green dextran (Mr 10,000). Ca2+ stores were evoked by the addition of 5 μM Ca2+ ionophore, monitored using a computer-controlled photo-multiplier system, and measured as relative fluorescence units (RFU) by normalizing fluorescence against baseline fluorescence. In lamb and ewe, differences in electrical features and calcium dynamics between GV (n = 36 and 17) and MII (n = 42 and 32) oocytes were tested by ANOVA and expressed as mean ± SEM. Resting potential was higher at MII than GV stages (−15.2 ± 0.9 vs. −12.1 ± 1.1 mV, respectively; P < 0.02) but it did not differ between animal age. GV stage and ewe showed either a higher steady-state conductance (25.4 ± 0.2 vs. 11.7 ± 0.2 nS and 21.7 ± 0.2 vs. 15.4 ± 0.2 nS, respectively; P < 0.01) or L-type Ca2+ channels (9.7 ± 1.4 vs. 2.7 ± 1.3 pA and 9.2 ± 1.5 vs. 3.2 ± 1.1 pA, respectively; P < 0.01). No differences were found between resting potential peaks yielded after Ca2+ ionophore exposure but a higher ion activation current was found in lamb oocytes (489 ± 56 vs. 300 ± 73 pA; P < 0.05). Ca2+ stores did not differ between animal age but they were larger at MII than at GV stage (0.70 ± 0.07 vs. 0.44 ± 0.07 RFU; P < 0.01). These results supply further information on both reproductive biology in ovine species and the physiology of oocytes collected from juvenile and adult individuals. This work was supported by Italian Ministry of University and Research (MIUR) COFIN 2002 Project.
48
Kuksis, Markus, and Alastair V. Ferguson. "Actions of a hydrogen sulfide donor (NaHS) on transient sodium, persistent sodium, and voltage-gated calcium currents in neurons of the subfornical organ." Journal of Neurophysiology 114, no. 3 (September 2015): 1641–51. http://dx.doi.org/10.1152/jn.00252.2015.
Full textAbstract:
Hydrogen sulfide (H2S) is an endogenously found gasotransmitter that has been implicated in a variety of beneficial physiological functions. This study was performed to investigate the cellular mechanisms underlying actions of H2S previously observed in subfornical organ (SFO), where H2S acts to regulate blood pressure through a depolarization of the membrane and an overall increase in the excitability of SFO neurons. We used whole cell patch-clamp electrophysiology in the voltage-clamp configuration to analyze the effect of 1 mM NaHS, an H2S donor, on voltage-gated potassium, sodium, and calcium currents. We observed no effect of NaHS on potassium currents; however, both voltage-gated sodium currents (persistent and transient) and the N-type calcium current had a depolarized activation curve and an enhanced peak-induced current in response to a series of voltage-step and ramp protocols run in the control and NaHS conditions. These effects were not responsible for the previously observed depolarization of the membrane potential, as depolarizing effects of H2S were still observed following block of these conductances with tetrodotoxin (5 μM) and ω-conotoxin-GVIA (100 nM). Our studies are the first to investigate the effect of H2S on a variety of voltage-gated conductances in a single brain area, and although they do not explain mechanisms underlying the depolarizing actions of H2S on SFO neurons, they provide evidence of potential mechanisms through which this gasotransmitter influences the excitability of neurons in this important brain area as a consequence of the modulation of multiple ion channels.
49
Carlson, Noel G., Whitney A. Wieggel, Jian Chen, Annalisa Bacchi, Scott W. Rogers, and Lorise C. Gahring. "Inflammatory Cytokines IL-1α, IL-1β, IL-6, and TNF-α Impart Neuroprotection to an Excitotoxin Through Distinct Pathways." Journal of Immunology 163, no. 7 (October 1, 1999): 3963–68. http://dx.doi.org/10.4049/jimmunol.163.7.3963.
Full textAbstract:
Abstract The proinflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α are produced within the CNS, and, similar to the periphery, they have pleotrophic and overlapping functions. We have shown previously that TNF-α increases neuronal survival to a toxic influx of calcium mediated through neuronal N-methyl-d-aspartic acid (NMDA) glutamate-gated ion channels. This process, termed excitotoxicity, is a major contributor to neuronal death following ischemia or stroke. Neuroprotection by this cytokine requires both activation of the p55/TNF receptor type I and the release of TNF-α from neurons, and it is inhibited by the plant alkaloid nicotine. Here, we report that other inflammatory cytokines (IL-1α, IL-1β, and IL-6) are also neuroprotective to excessive NMDA challenge in our system. Neuroprotection provided by IL-1 is distinct from TNF-α because it is inhibited by IL-1 receptor antagonist; it is not antagonized by nicotine, but it is inhibited by a neutralizing Ab to nerve growth factor (NGF). Similar to IL-1, IL-6-mediated neuroprotection is also antagonized by pretreatment with IL-1 receptor antagonist and it is not affected by nicotine. However, neutralizing anti-NGF only partially blocks IL-6-mediated protection. These studies support an important role for distinct but overlapping neuroprotective cytokine effects in the CNS.
50
Nandakumar, DN, P. Ramaswamy, C. Prasad, D. Srinivas, and K. Goswami. "Glioblastoma invasion and NMDA receptors: A novel prospect." Physiology International 106, no. 3 (September 2019): 250–60. http://dx.doi.org/10.1556/2060.106.2019.22.
Full textAbstract:
Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.