To see the other types of publications on this topic, follow the link: Calcium transient duration.
Journal articles on the topic 'Calcium transient duration'
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 'Calcium transient duration.'
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
Ratan, R. R., F. R. Maxfield, and M. L. Shelanski. "Long-lasting and rapid calcium changes during mitosis." Journal of Cell Biology 107, no. 3 (September 1, 1988): 993–99. http://dx.doi.org/10.1083/jcb.107.3.993.
Full textAbstract:
A more complete understanding of calcium's role in cell division requires knowledge of the timing, magnitude, and duration of changes in cytoplasmic-free calcium, [Ca2+]i, associated with specific mitotic events. To define the temporal relationship of changes in [Ca2+]i to cellular and chromosomal movements, we have measured [Ca2+]i every 6-7 s in single-dividing Pt K2 cells using fura-2 and microspectrophotometry, coupling each calcium measurement with a bright-field observation. In the 12 min before discernable chromosome some separation, 90% of metaphase cells show at least one transient of increased [Ca2+]i, 72% show their last transient within 5 min, and a peak of activity is seen at 3 min before chromosome separation. The mean [Ca2+]i of the metaphase transients is 148 +/- 31 nM (61 transients in 35 cells) with an average duration of 21 +/- 14 s. The timing of these increases makes it unlikely that these transient increases in [Ca2+]i are acting directly to trigger the start of anaphase. However, it is possible that a transient rise in calcium during late metaphase is part of a more complex progression to anaphase. In addition to these transient changes, a gradual increase in [Ca2+]i was observed starting in late anaphase. Within the 2 min surrounding cytokinesis onset, 82% of cells show a transient increase in [Ca2+]i to 171 +/- 48 nM (53 transients in 32 cells). The close temporal correlation of these changes with cleavage is consistent with a more direct role for calcium in this event, possibly by activating the contractile system. To assess the specificity of these changes to the mitotic cycle, we examined calcium changes in interphase cells. Two-thirds of interphase cells show no transient increases in calcium with a mean [Ca2+]i of 100 +/- 18 nM (n = 12). However, one-third demonstrate dramatic and repeated transient increases in [Ca2+]i. The mean peak [Ca2+]i of these transients is 389 +/- 70 nM with an average duration of 77 s. The necessity of any of these transient changes in calcium for the completion of mitotic or interphase activities remains under investigation.
2
Liu, Y., S. L. Carroll, M. G. Klein, and M. F. Schneider. "Calcium transients and calcium homeostasis in adult mouse fast-twitch skeletal muscle fibers in culture." American Journal of Physiology-Cell Physiology 272, no. 6 (June 1, 1997): C1919—C1927. http://dx.doi.org/10.1152/ajpcell.1997.272.6.c1919.
Full textAbstract:
Skeletal muscle fibers enzymatically dissociated from adult mouse flexor digitorum brevis muscles were maintained in culture for up to 8 days. After various times in culture, fibers were loaded with fura 2, and Ca2+ transients for trains of 1, 5, and 10 action potentials (100 Hz) triggered by external electrical stimulation were calculated from fluorescence ratio records corrected for noninstantaneous reaction of fura 2 with Ca2+. The decay rate constants of Ca2+ transients decreased with increasing stimulation duration, indicating a slowing of the Ca(2+)-removal properties with increased stimulation duration. After 6 days in culture, Ca2+ decay rate constants decreased dramatically for all stimulation durations and the differences in decay rate constants among 1, 5, and 10 pulses became smaller. Intracellular parvalbumin content measured by single-fiber immunofluorescence decreased with time in culture in parallel with the decrease in the decay rate constant of Ca2+ transients. Our results suggest that there is a correlation between parvalbumin content and the decay rate constant of the Ca2+ transient.
3
Vyshedskiy, Andrey, and Jen-Wei Lin. "Presynaptic Ca2+ Influx at the Inhibitor of the Crayfish Neuromuscular Junction: A Photometric Study at a High Time Resolution." Journal of Neurophysiology 83, no. 1 (January 1, 2000): 552–62. http://dx.doi.org/10.1152/jn.2000.83.1.552.
Full textAbstract:
Presynaptic calcium influx at the inhibitor of the crayfish neuromuscular junction was investigated by measuring fluorescence transients generated by calcium-sensitive dyes. This approach allowed us to correlate presynaptic calcium influx with transmitter release at a high time resolution. Systematic testing of the calcium indicators showed that only low-affinity dyes, with affinities in the range of micromolar, should be used to avoid saturation of dye binding and interference with transmitter release. Presynaptic calcium influx was regulated by slowly increasing the duration of the action potential through progressive block of potassium channels. The amplitude of the calcium transient, measured from a cluster of varicosities, was linearly related to the duration of the action potential with a slope of 1.2. Gradual changes in potassium channel block allowed us to estimate the calcium cooperativity of transmitter release over a 10-fold range in presynaptic calcium influx. Calcium cooperativity measured here exhibited one component with an average value of 3.1. Inspection of simultaneously recorded presynaptic calcium transients and inhibitory postsynaptic currents (IPSCs) showed that prolonged action potentials were associated with a slow rising phase of presynaptic calcium transients, which were matched by a slow rate of rise of IPSCs. The close correlation suggests that fluorescence transients provide information on the rate of calcium influx. Because there is an anatomic mismatch between the presynaptic calcium transient, measured from a cluster of varicosities, and IPSC, measured with two-electrode voltage clamp, macropatch recording was used to monitor inhibitory postsynaptic responses from the same cluster of varicosities from which the calcium transient was measured. Inhibitory postsynaptic responses recorded with the macropatch method exhibited a faster rising phase than that recorded with two-electrode voltage clamp. This difference could be attributed to slight asynchrony of transmitter release due to action potential conduction along fine branches. In conclusion, this report shows that fluorescence transients generated by calcium-sensitive dyes can provide insights to the properties of presynaptic calcium influx, and its correlation with transmitter release, at a high time resolution.
4
Gidö, Gunilla, Kenichiro Katsura, Tibor Kristian, and Bo K. Siesjö. "Influence of Plasma Glucose Concentration on Rat Brain Extracellular Calcium Transients during Spreading Depression." Journal of Cerebral Blood Flow & Metabolism 13, no. 1 (January 1993): 179–82. http://dx.doi.org/10.1038/jcbfm.1993.21.
Full textAbstract:
The objective of this study was to establish whether tissues that are energy compromised, but not energy depleted, demonstrate exaggerated calcium transients when subjected to membrane depolarizations of the spreading depression (SD) type. Anesthetized and artificially ventilated rats were given insulin in order to induce progressively lower plasma glucose concentrations. Spreading depression was elicited by local application of KCl; extracellular calcium concentration (Ca2+e) as well as direct current (DC) potential were recorded. When plasma glucose concentration fell below ∼3 m M, the duration of the Ca2+e transient gradually increased to values exceeding 500% of control. The increase was associated with a corresponding increase in the duration of the DC potential shift, but the amplitude of the Ca2+e transient did not change. It is concluded that a restriction of glucose (or oxygen) supply, as occurs in hypoglycemia (or hypoxia), prolongs the calcium transient associated with depolarization of the SD type, even though tissue phosphocreatine and ATP concentrations are normal. The results support the contention that repeated depolarizations, occurring in the penumbral zone of a focal ischemic lesion, could lead to calcium-related damage.
5
Wang, C., and Z. Machaty. "189 CHARACTERIZATION OF THE FIRST SPERM-INDUCED CALCIUM TRANSIENT IN PIG OOCYTES." Reproduction, Fertility and Development 28, no. 2 (2016): 225. http://dx.doi.org/10.1071/rdv28n2ab189.
Full textAbstract:
Fertilization in mammals is associated with repetitive elevations in the oocytes’ intracellular free calcium concentration. The elevations are triggered by the fertilizing sperm and are responsible for stimulating embryo development. In mouse oocytes, the sperm-induced calcium signal starts with a calcium rise that is larger and longer in duration than any succeeding transients. It also has unique characteristics: it begins with a rapid increase for 2–3 s followed by a shoulder, which is an inflection point that represents a brief decline in the rise of calcium levels. Once calcium level reaches its maximum, it decreases but remains elevated for several minutes while it is superimposed by several smaller calcium spikes. In bovine oocytes the situation is somewhat different. In this species, the first sperm-induced calcium transient is larger than the additional spikes but it lacks the sustained elevation phase and is not superimposed by small calcium rises. In the present study our purpose was to characterise the first sperm-induced calcium transient in pig oocytes. Oocytes were obtained from ovaries of prepubertal gilts collected at an abattoir and matured in vitro for 44 h. Mature oocytes were loaded with the calcium indicator dye fura-2; subsequently, they were either IVF or used for intracytoplasmic sperm injection (ICSI). Changes in their intracellular free calcium concentration were then immediately monitored using InCyt Im2, a dual-wavelength fluorescence imaging system. Characteristics of the first transients (including amplitude and duration) were compared to those of the additional ones using Student’s t-test. We found that in oocytes that underwent IVF (n = 11), the oscillations started 83.4 ± 23.2 min after adding the sperm to the oocytes. In the ICSI group (n = 10 oocytes) the calcium oscillations started sooner, 27.1 ± 17.7 min after injection. The average peak amplitude and the mean interval between the calcium transients varied among individual oocytes, but no significant differences were found between the IVF and ICSI groups (which on average were fluorescence ratio of 2.6 ± 1.1 and 23.5 ± 11.4 min, respectively; P > 0.1). The oscillation patterns showed slight differences between individual oocytes in terms of spike frequency, which has been described before and may be due to variations in the amount of sperm-derived activating factor present in the ooplasm. Most importantly, in all oocytes measured, the initial calcium spike showed no differences when compared to subsequent calcium transients: its amplitude and duration was similar to the additional transients. This points at potential species-specific differences in the regulation of calcium signalling in oocytes and provides essential information for the better understanding of the fertilization process. This work was supported by Agriculture and Food Research Initiative Competitive Grant 2011–67015–30006 from the USDA National Institute of Food and Agriculture.
6
Hartmann, T., M. Kondo, H. Mochizuki, A. S. Verkman, and J. H. Widdicombe. "Calcium-dependent regulation of Cl secretion in tracheal epithelium." American Journal of Physiology-Lung Cellular and Molecular Physiology 262, no. 2 (February 1, 1992): L163—L168. http://dx.doi.org/10.1152/ajplung.1992.262.2.l163.
Full textAbstract:
In primary cultures of dog tracheal epithelium, isoproterenol produced a transient increase in short-circuit current (Isc) (duration 30 s; maximal increase, 32 +/- 5 microA/cm2). This was followed by a more slowly developing sustained increase (9 +/- 3 microA/cm2), which mimicked the response to N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP). The transient and sustained responses had dissociation constants for isoproterenol of 2 x 10(-8) and 2 x 10(-9) M, respectively. Bradykinin (in the presence of indomethacin), substance P, histamine, and thrombin produced only transient increases in Isc. The time courses of these transients closely paralleled changes in concentration of intracellular Ca ([Ca2+]i) as measured with fura 2. For different mediators, there was a significant correlation between the maximal transient increase in Isc and the maximal increase in [Ca2+]i. The transients in Isc were not associated with elevation of adenosine 3',5'-cyclic monophosphate (cAMP) and were unaffected by pretreatment with DBcAMP, which abolishes the steady-state increase in response to isoproterenol. Both the transient increases in Isc and [Ca2+]i were inhibited by pretreatment with the Ca chelator 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate abolished the transient increases in [Ca2+]i and Isc in response to isoproterenol but not to bradykinin. These results provide evidence that 1) isoproterenol and bradykinin elevate [Ca2+]i by different mechanisms, and 2) Ca elevation is associated with a transient increase in Isc, whereas increased cAMP is associated with a smaller sustained increase.
7
Chaigne, Sebastien, Guillaume Cardouat, Julien Louradour, Fanny Vaillant, Sabine Charron, Frederic Sacher, Thomas Ducret, Romain Guinamard, Edward Vigmond, and Thomas Hof. "Transient receptor potential vanilloid 4 channel participates in mouse ventricular electrical activity." American Journal of Physiology-Heart and Circulatory Physiology 320, no. 3 (March 1, 2021): H1156—H1169. http://dx.doi.org/10.1152/ajpheart.00497.2020.
Full textAbstract:
Transient receptor potential vanilloid 4 (TRPV4) is expressed at the membrane of mouse ventricular myocytes and colocalizes with non-T-tubular L-type calcium channels. Deletion of trpv4 gene in mice results in shortened QT interval on electrocardiogram and reduced action potential duration of ventricular myocytes. Pharmacological activation of TRPV4 channel leads to increased action potential duration and increased calcium transient amplitude in trpv4−/− but not in trpv4−/− ventricular myocytes. To the contrary, TRPV4 channel pharmacological inhibition reduces action potential duration in trpv4+/+ but not in trpv4−/− myocytes. Integration of TRPV4 channel in a computational model of mouse action potential shows that the channel carries an inward current contributing to slowing down action potential repolarization and to increase calcium transient amplitude, similarly to what is observed experimentally. This study highlights for the first time the involvement of TRPV4 channel in ventricular electrical activity.
8
Schneider, Eve R., Eugene F. Civillico, and Samuel S. H. Wang. "Calcium-based dendritic excitability and its regulation in the deep cerebellar nuclei." Journal of Neurophysiology 109, no. 9 (May 1, 2013): 2282–92. http://dx.doi.org/10.1152/jn.00925.2012.
Full textAbstract:
The deep cerebellar nuclei (DCN) convey the final output of the cerebellum and are a major site of activity-dependent plasticity. Here, using patch-clamp recording and two-photon calcium imaging in rat brain slices, we demonstrate that DCN dendrites exhibit three hallmarks of active amplification of electrical signals. First, they produce calcium transients with rise times of tens of milliseconds, comparable in amplitude and duration to calcium spikes in other neurons. Second, calcium signal amplitudes are undiminished along the length of dendrites to the farthest distances from the soma. Third, they can generate calcium signals even in the presence of tetrodotoxin, a sodium channel blocker that abolishes somatic action potential initiation. DCN calcium transients do require the action of T-type calcium channels, a common voltage-gated conductance in excitable dendrites. Dendritic calcium influx was evoked by release from hyperpolarization, peaked within tens of milliseconds, and was observed in both transient- and weak-rebound-firing neurons. In a survey across the DCN, transient-burst rebound firing, which was accompanied by the most rapid calcium flux, was more common in lateral nucleus than in interpositus nucleus and was not seen in medial nucleus. Rebound firing and calcium transients were not present in animals shipped 1–3 days before recording, a condition associated with elevated maternal and pup corticosterone and reduced pup body weight. Rebounds could be restored by the protein kinase C activator phorbol 12-myristate-13-acetate. Thus local calcium-based dendritic excitability supports a stage of presomatic amplification that is under regulation by stress and neuromodulatory influence.
9
Roome, Chris J., Emmet M. Power, and Ruth M. Empson. "Transient reversal of the sodium/calcium exchanger boosts presynaptic calcium and synaptic transmission at a cerebellar synapse." Journal of Neurophysiology 109, no. 6 (March 15, 2013): 1669–80. http://dx.doi.org/10.1152/jn.00854.2012.
Full textAbstract:
The sodium/calcium exchanger (NCX) is a widespread transporter that exchanges sodium and calcium ions across excitable membranes. Normally, NCX mainly operates in its “forward” mode, harnessing the electrochemical gradient of sodium ions to expel calcium. During membrane depolarization or elevated internal sodium levels, NCX can instead switch the direction of net flux to expel sodium and allow calcium entry. Such “reverse”-mode NCX operation is frequently implicated during pathological or artificially extended periods of depolarization, not during normal activity. We have used fast calcium imaging, mathematical simulation, and whole cell electrophysiology to study the role of NCX at the parallel fiber-to-Purkinje neuron synapse in the mouse cerebellum. We show that nontraditional, reverse-mode NCX activity boosts the amplitude and duration of parallel fiber calcium transients during short bursts of high-frequency action potentials typical of their behavior in vivo. Simulations, supported by experimental manipulations, showed that accumulation of intracellular sodium drove NCX into reverse mode. This mechanism fueled additional calcium influx into the parallel fibers that promoted synaptic transmission to Purkinje neurons for up to 400 ms after the burst. Thus we provide the first functional demonstration of transient and fast NCX-mediated calcium entry at a major central synapse. This unexpected contribution from reverse-mode NCX appears critical for shaping presynaptic calcium dynamics and transiently boosting synaptic transmission, and is likely to optimize the accuracy of cerebellar information transfer.
10
Katra, Rodolphe P., Etienne Pruvot, and Kenneth R. Laurita. "Intracellular calcium handling heterogeneities in intact guinea pig hearts." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 2 (February 2004): H648—H656. http://dx.doi.org/10.1152/ajpheart.00374.2003.
Full textAbstract:
Regional heterogeneities of ventricular repolarizing currents and their role in arrhythmogenesis have received much attention; however, relatively little is known regarding heterogeneities of intracellular calcium handling. Because repolarization properties and contractile function are heterogeneous from base to apex of the intact heart, we hypothesize that calcium handling is also heterogeneous from base to apex. To test this hypothesis, we developed a novel ratiometric optical mapping system capable of measuring calcium fluorescence of indo-1 at two separate wavelengths from 256 sites simultaneously. With the use of intact Langendorff-perfused guinea pig hearts, ratiometric calcium transients were recorded under normal conditions and during administration of known inotropic agents. Ratiometric calcium transients were insensitive to changes in excitation light intensity and fluorescence over time. Under control conditions, calcium transient amplitude near the apex was significantly larger (60%, P < 0.01) compared with the base. In contrast, calcium transient duration was significantly longer (7.5%, P < 0.03) near the base compared with the apex. During isoproterenol (0.05 μM) and verapamil (2.5 μM) administration, ratiometric calcium transients accurately reflected changes in contractile function, and, the direction of base-to-apex heterogeneities remained unchanged compared with control. Ratiometric optical mapping techniques can be used to accurately quantify heterogeneities of calcium handling in the intact heart. Significant heterogeneities of calcium release and sequestration exist from base to apex of the intact heart. These heterogeneities are consistent with base-to-apex heterogeneities of contraction observed in the intact heart and may play a role in arrhythmogenesis under abnormal conditions.
11
Xie, Lai-Hua, and James N. Weiss. "Arrhythmogenic consequences of intracellular calcium waves." American Journal of Physiology-Heart and Circulatory Physiology 297, no. 3 (September 2009): H997—H1002. http://dx.doi.org/10.1152/ajpheart.00390.2009.
Full textAbstract:
Intracellular Ca2+ (Cai2+) waves are known to cause delayed afterdepolarizations (DADs), which have been associated with arrhythmias in cardiac disease states such as heart failure, catecholaminergic polymorphic ventricular tachycardia, and digitalis toxicity. Here we show that, in addition to DADs, Cai2+ waves also have other consequences relevant to arrhythmogenesis, including subcellular spatially discordant alternans (SDA, in which the amplitude of the local Cai2+ transient alternates out of phase in different regions of the same cell), sudden repolarization changes promoting the dispersion of refractoriness, and early afterdepolarizations (EADs). Cai2+ was imaged using a charge-coupled device-based system in fluo-4 AM-loaded isolated rabbit ventricular myocytes paced at constant or incrementally increasing rates, using either field stimulation, current clamp, or action potential (AP) clamp. Cai2+ waves were induced by Bay K 8644 (50 nM) + isoproterenol (100 nM), or low temperature. When pacing was initiated during a spontaneous Cai2+ wave, SDA occurred abruptly and persisted during pacing. Similarly, during rapid pacing, SDA typically arose suddenly from spatially concordant alternans, due to an abrupt phase reversal of the subcellular Cai2+ transient in a region of the myocyte. Cai2+ waves could be visualized interspersed with AP-triggered Cai2+ transients, producing a rich variety of subcellular Cai2+ transient patterns. With free-running APs, complex Cai2+ release patterns were associated with DADs, EADs, and sudden changes in AP duration. These findings link Cai2+ waves directly to a variety of arrhythmogenic phenomena relevant to the intact heart.
12
Bailey, B. A., and S. R. Houser. "Sarcoplasmic reticulum-related changes in cytosolic calcium in pressure-overload-induced feline LV hypertrophy." American Journal of Physiology-Heart and Circulatory Physiology 265, no. 6 (December 1, 1993): H2009—H2016. http://dx.doi.org/10.1152/ajpheart.1993.265.6.h2009.
Full textAbstract:
Alterations in Ca2+ homeostasis that involve the sarcoplasmic reticulum (SR) were studied in feline left ventricular (LV) myocytes isolated from hearts with LV hypertrophy induced by slow, progressive pressure overload. At death, severe hypertrophy was evidenced by increased heart weight-to-body weight ratio (8.4 +/- 0.6 vs. 4.2 +/- 0.2 g/kg in controls). Steady-state Ca2+ transients (measured as. indo 1 fluorescence at 410 nm/480 nm; I410/I480) in LV hypertrophy (LVH) myocytes had diminished peak amplitudes (I410/I480 2.28 +/- 0.07 vs. 2.53 +/- 0.07 in controls) and prolonged durations (0.75 +/- 0.03 vs. 0.59 +/- 0.02 s in controls). The magnitude of shortening was reduced and the contractile duration was prolonged in LVH myocytes. The idea that changes in SR function are responsible for these alterations in the Ca2+ transient was tested by studying two aspects of SR-related Ca2+ homeostasis. Restitution of releasable SR Ca2+ was studied by measuring indo 1 transients and contractions during premature beats. The time course of restitution of both the indo 1 transient and contraction of hypertrophy myocytes was significantly slower than in controls. These data suggest that restitution of releasable SR Ca2+ is slowed in hypertrophy myocytes. The reduction of the indo 1 transient and contraction in beats following long rest periods (rest decay) was measured to determine the rate of Ca2+ loss from the SR. Rest decay was significantly (P < 0.05) more pronounced in hypertrophy myocytes, suggesting that Ca2+ loss from the SR is accelerated in these myocytes. (ABSTRACT TRUNCATED AT 250 WORDS)
13
Yan, L. Y., C. Wang, H. L. Luo, and Z. Machaty. "184 INHIBITION OF CALCIUM EFFLUX EXTENDS THE DURATION OF CALCIUM SIGNALS IN PIG OOCYTES." Reproduction, Fertility and Development 24, no. 1 (2012): 204. http://dx.doi.org/10.1071/rdv24n1ab184.
Full textAbstract:
Calcium signaling involves the transient elevation in the intracellular free-calcium concentration, which is responsible for controlling a great number of biological functions. In many cell types, a signal is generated when calcium stored in the endoplasmic reticulum is released into the cytoplasm, followed by an influx of calcium across the plasma membrane. At the same time, calcium is removed from the cytosol by ATPases, which pump it back into the intracellular store or out of the cell. The size of the calcium signal is thus determined by the amount of calcium moving into and out of the cytoplasm. In the present study, we investigated the effect of inhibiting the movement of calcium across the plasma membrane on a calcium-signal that was artificially induced in pig oocytes. In vitro-matured pig oocytes were loaded with the calcium-indicator dye, fura-2. The release of calcium from the cytoplasmic stores was stimulated by adding ethanol at a final concentration of 7% and changes in the intracellular free-calcium levels were monitored by using InCyt Im2, a dual-wavelength fluorescence imaging system. In the control group, fluorescent measurements were performed in the presence of extracellular calcium. In additional treatment groups, the ethanol treatment was performed in (1) a calcium-free medium (prevents calcium influx); (2) the presence of 1 mM gadolinium (limits calcium fluxes across the plasma membrane in both directions); and (3) the presence of gadolinium in a calcium-free medium. In each group, 15 oocytes were measured; the data were subjected to 1-way ANOVA and differences between treatment means were compared by the Tukey's test. We found that in control oocytes, 7% ethanol induced a rise of 722.1 ± 49.2 nM in the cytoplasmic calcium levels and the average duration of the calcium transient was 309.1 ± 11.3 s. In the calcium-free medium, this increase was significantly smaller (only 117.9 ± 4.8 nM; P < 0.01), probably because the calcium release was not followed by an influx of calcium across the plasma membrane. In the presence of 1 mM gadolinium in the regular calcium-containing medium, the intracellular calcium levels climbed by 278.8 ± 45.4 nM and dropped to baseline levels only after 773.3 ± 79.9 s. Finally, in the calcium-free medium and in the presence of 1 mM gadolinium, 7% ethanol induced only a small rise (64.5 ± 6.3 nM) in the cytoplasmic calcium levels. These latter increases were both significantly lower (P < 0.01) compared to that in the control group. The results indicate that (1) intracellular calcium signals are sustained by a calcium influx from the extracellular medium and (2) preventing calcium efflux extends the duration of the cytoplasmic calcium elevation in the oocyte. This may have relevance in the manipulation of intracellular calcium levels in oocytes for the development of novel parthenogenetic activation methods.
14
Crossley, I., T. Whalley, and M. Whitaker. "Guanosine 5'-thiotriphosphate may stimulate phosphoinositide messenger production in sea urchin eggs by a different route than the fertilizing sperm." Cell Regulation 2, no. 2 (February 1991): 121–33. http://dx.doi.org/10.1091/mbc.2.2.121.
Full textAbstract:
We show that microinjecting guanosine-5'-thiotriphosphate (GTP gamma S) into unfertilized sea urchin eggs generates an intracellular free calcium concentration [( Ca]i) transient apparently identical in magnitude and duration to the calcium transient that activates the egg at fertilization. The GTP gamma S-induced transient is blocked by prior microinjection of the inositol trisphosphate (InsP3) antagonist heparin. GTP gamma S injection also causes stimulation of the egg's Na+/H+ antiporter via protein kinase C, even in the absence of a [Ca]i increase. These data suggest that GTP gamma S acts by stimulating the calcium-independent production of the phosphoinositide messengers InsP3 and diacylglycerol (DAG). However, the fertilization [Ca]i transient is not affected by heparin, nor can the sperm cause calcium-independent stimulation of protein kinase C. It seems that the bulk of InsP3 and DAG production at fertilization is triggered by the [Ca]i transient, not by the sperm itself. GDP beta S, a G-protein antagonist, does not affect the fertilization [Ca]i transient. Our findings do not support the idea that signal transduction at fertilization operates via a G-protein linked directly to a plasma membrane sperm receptor.
15
Kapur, Sunil, Gary L. Aistrup, Rohan Sharma, James E. Kelly, Rishi Arora, Jiabo Zheng, Mitra Veramasuneni, Alan H. Kadish, C. William Balke, and J. Andrew Wasserstrom. "Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats." American Journal of Physiology-Heart and Circulatory Physiology 299, no. 6 (December 2010): H1843—H1853. http://dx.doi.org/10.1152/ajpheart.00623.2010.
Full textAbstract:
Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca2+ cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca2+ transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5–9 mo compared with 6 mo. Ca2+ transient duration increased at 9 mo in SHRs, indicating changes in Ca2+ reuptake during decompensation. Cell-to-cell variability in Ca2+ transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca2+ transient kinetics during disease progression. Vulnerability to intercellular concordant Ca2+ alternans increased at 9–22 mo in SHRs and was mirrored by a slowing in Ca2+ transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca2+ alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca2+ waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca2+ cycling develop in SHRs long before symptoms of HF occur. Defective Ca2+ cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca2+ alternans and Ca2+ wave activity, thus increasing the propensity for arrhythmogenesis in HF.
16
Fuchs, Andreas, Marcel Rigaud, and Quinn H. Hogan. "Painful Nerve Injury Shortens the Intracellular Ca2+ Signal in Axotomized Sensory Neurons of Rats." Anesthesiology 107, no. 1 (July 1, 2007): 106–16. http://dx.doi.org/10.1097/01.anes.0000267538.72900.68.
Full textAbstract:
Abstract Background: Neuropathic pain is inadequately treated and poorly understood at the cellular level. Because intracellular Ca2+ signaling critically regulates diverse neuronal functions, the authors examined effects of peripheral nerve injury on the Ca2+ transient that follows neuronal activation. Methods: Cytoplasmic Ca2+ levels were recorded by digital microfluorometry from dissociated dorsal root ganglion neurons of hyperalgesic animals after ligation of the fifth lumbar spinal nerve and control animals. Neurons were activated by field stimulation or by K+ depolarization. Results: Transients in presumptively nociceptive, small, capsaicin-sensitive neurons were diminished after axotomy, whereas transient amplitude increased in axotomized nonnociceptive neurons. Axotomy diminished the upward shift in resting calcium after transient recovery. In contrast, nociceptive neurons adjacent to axotomy acquired increased duration of the transient and greater baseline shift after K+ activation. Transients of nonnociceptive neurons adjacent to axotomy showed no changes after injury. In nociceptive neurons from injured rats that did not develop hyperalgesia, transient amplitude and baseline offset were large after axotomy, whereas transient duration in the adjacent neurons was shorter compared with neurons excised from hyperalgesic animals, which show normalization of these features. Conclusions: A diminished Ca2+ signal in axotomized neurons may be in part due to loss of Ca2+ influx through voltage-gated Ca2+ channels. The upward shift in resting Ca2+ level after activation, which is diminished after axotomy in presumed nociceptive neurons, is a previously unrecognized aspect of neuronal plasticity. These changes in the critical Ca2+ signal may mediate various injury-related abnormalities in Ca2+-dependent neuronal.
17
Cinelli, Angel R., Dalton Wang, Ping Chen, Weimin Liu, and Mimi Halpern. "Calcium Transients in the Garter Snake Vomeronasal Organ." Journal of Neurophysiology 87, no. 3 (March 1, 2002): 1449–72. http://dx.doi.org/10.1152/jn.00651.2001.
Full textAbstract:
The signaling cascade involved in chemosensory transduction in the VN organ is incompletely understood. In snakes, the response to nonvolatile prey chemicals is mediated by the vomeronasal (VN) system. Using optical techniques and fluorescent Ca2+ indicators, we found that prey-derived chemoattractants produce initially a transient cytosolic accumulation of [Ca2+]i in the dendritic regions of VN neurons via two pathways: Ca2+release from IP3-sensitive intracellular stores and, to a lesser extent, Ca2+ influx through the plasma membrane. Both components seem to be dependent on IP3 production. Chemoattractants evoke a short-latency Ca2+ elevation even in the absence of extracellular Ca2+, suggesting that in snake VN neurons, Ca2+ release from intracellular stores is independent of a preceding Ca2+ influx, and both components are activated in parallel during early stages of chemosensory transduction. Once the response develops in apical dendritic segments, other mechanisms can also contribute to the amplification and modulation of these chemoattractant-mediated cytosolic Ca2+ transients. In regions close to the cell bodies of the VN neurons, the activation of voltage-sensitive Ca2+ channels and a Ca2+-induced Ca2+ release from intracellular ryanodine-sensitive stores secondarily boost initial cytosolic Ca2+ elevations increasing their magnitude and durations. Return of intracellular Ca2+ to prestimulation levels appears to involve a Ca2+ extrusion mediated by a Na+/Ca2+ exchanger mechanism that probably plays an important role in limiting the magnitude and duration of the stimulation-induced Ca2+ transients.
18
MacGowan, Guy A., Congwu Du, Douglas B. Cowan, Christof Stamm, Francis X. McGowan, R. John Solaro, Alan P. Koretsky, and Pedro J. Del Nido. "Ischemic dysfunction in transgenic mice expressing troponin I lacking protein kinase C phosphorylation sites." American Journal of Physiology-Heart and Circulatory Physiology 280, no. 2 (February 1, 2001): H835—H843. http://dx.doi.org/10.1152/ajpheart.2001.280.2.h835.
Full textAbstract:
To determine the in vivo functional significance of troponin I (TnI) protein kinase C (PKC) phosphorylation sites, we created a transgenic mouse expressing mutant TnI, in which PKC phosphorylation sites at serines-43 and -45 were replaced by alanine. When we used high-perfusate calcium as a PKC activator, developed pressures in transgenic (TG) perfused hearts were similar to wild-type (WT) hearts ( P = not significant, NS), though there was a 35% and 32% decrease in peak-systolic intracellular calcium ( P < 0.01) and diastolic calcium ( P < 0.005), respectively. The calcium transient duration was prolonged in the TG mice also (12–27%, ANOVA, P < 0.01). During global ischemia, TG hearts developed ischemic contracture to a greater extent than WT hearts (41 ± 18 vs. 69 ± 10 mmHg, perfusate calcium 3.5 mM, P < 0.01). In conclusion, expression of mutant TnI lacking PKC phosphorylation sites results in a marked alteration in the calcium-pressure relationship, and thus susceptibility to ischemic contracture. The reduced intracellular calcium and prolonged calcium transients suggests that a potent feedback mechanism exists between the myofilament and the processes controlling calcium homeostasis.
19
Clusin, William T. "Mechanisms of calcium transient and action potential alternans in cardiac cells and tissues." American Journal of Physiology-Heart and Circulatory Physiology 294, no. 1 (January 2008): H1—H10. http://dx.doi.org/10.1152/ajpheart.00802.2007.
Full textAbstract:
Alternation of cardiac action potential duration (APD) from beat to beat and concurrent alternation of the amplitude of the calcium transient are regarded as important arrhythmia mechanisms. These phenomena are causally interrelated and can be reliably evoked by an increase in beat frequency or by ischemia. The first part of this historical review deals with the physiology of APD alternans. Sections recounting the evolution of knowledge about calcium-activated ion currents and calcium transient alternans are interspersed among sections describing the growth of the so-called “restitution hypothesis,” which involves time-dependent recovery of potassium channels (including their passage through pre-open states) as a function of diastolic interval. Major developments are generally in chronological order, but it is necessary to move back and forth between the two theories to respect the overall time line, which runs from about l965 to the present. The concluding two sections deal with the pathophysiology of calcium transient and APD alternans during ischemia, which may be the basis for out-of-hospital cardiac arrest during the initial stages of acute myocardial infarction.
20
Hishikawa, T., J. Y. Cheung, R. V. Yelamarty, and D. W. Knutson. "Calcium transients during Fc receptor-mediated and nonspecific phagocytosis by murine peritoneal macrophages." Journal of Cell Biology 115, no. 1 (October 1, 1991): 59–66. http://dx.doi.org/10.1083/jcb.115.1.59.
Full textAbstract:
Studies with populations of macrophages have produced conflicting results concerning the possibility that the concentration of intracellular ionized calcium [( Ca2+]i) may act as an important mediator for phagocytosis. Since asynchronous changes in [Ca2+]i in individual cells undergoing phagocytosis may be averaged to undetectability in population studies, we studied single adhering murine macrophages using fura-2 and our previously described digital imaging system. The proportion of macrophages phagocytosing IgG-coated latex beads was greater than for uncoated beads (percent phagocytosing cells: 71 +/- 7 vs. 27 +/- 7, P less than 0.01). Phagocytosis of IgG-coated and uncoated beads was always associated with a calcium transient that preceded the initiation of phagocytosis. No calcium transients were detected in cells that bound but did not phagocytose beads. Four major differences between Fc receptor-mediated and nonspecific phagocytosis were detected: (a) the duration of calcium transients was longer for nonspecific phagocytosis compared with Fc receptor-mediated phagocytosis (69.9 +/- 10.2 vs. 48.7 +/- 4.7 s, P less than 0.05) and the magnitude of calcium transients was less for nonspecific phagocytosis (178 +/- 43 vs. 349 +/- 53 nM, P less than 0.05); (b) removal of extracellular calcium abolished the calcium transients associated with nonspecific phagocytosis but had no effect on those associated with receptor-mediated phagocytosis; (c) in the absence of extracellular calcium, buffering intracellular calcium with a chelator reduced Fc receptor-mediated phagocytosis but had no additive inhibitory effect on nonspecific phagocytosis; and (d) inhibition of protein kinase C (PKC) with staurosporine inhibited nonspecific phagocytosis but had no effect on receptor-mediated phagocytosis. Our observations suggest that despite both types of phagocytosis being associated with intracellular calcium transients, the role played by intracellular calcium in the signaling pathways may differ for Fc receptor-mediated and nonspecific phagocytosis by elicited murine macrophages.
21
Whalley, T., A. McDougall, I. Crossley, K. Swann, and M. Whitaker. "Internal calcium release and activation of sea urchin eggs by cGMP are independent of the phosphoinositide signaling pathway." Molecular Biology of the Cell 3, no. 3 (March 1992): 373–83. http://dx.doi.org/10.1091/mbc.3.3.373.
Full textAbstract:
We show that microinjecting cyclic GMP (cGMP) into unfertilized sea urchin eggs activates them by stimulating a rise in the intracellular free calcium ion concentration ([Ca2+]i). The increase in [Ca2+]i is similar in both magnitude and duration to the transient that activates the egg at fertilization. It is due to mobilization of calcium from intracellular stores but is not prevented by the inositol trisphosphate (InsP3) antagonist heparin. Furthermore, cGMP does not stimulate the eggs Na+/H+ antiport when the [Ca2+]i transient is blocked by the calcium chelator bis-(O-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), suggesting that cGMP does not activate eggs by interacting with the their phosphoinositide signaling pathway. However, the [Ca2+]i increase and activation are prevented in eggs in which the InsP3-sensitive calcium stores have been emptied by the prior microinjection of the InsP3 analogue inositol 1,4,5-trisphosphorothioate. These data indicate that cGMP activates eggs by stimulating the release of calcium from an InsP3-sensitive calcium store via a novel, though unidentified, route independent of the InsP3 receptor.
22
Fisher, T. E., S. Levy, and L. K. Kaczmarek. "Transient changes in intracellular calcium associated with a prolonged increase in excitability in neurons of Aplysia californica." Journal of Neurophysiology 71, no. 3 (March 1, 1994): 1254–57. http://dx.doi.org/10.1152/jn.1994.71.3.1254.
Full textAbstract:
1. Transient stimulation of an afferent input to the bag cell neurons of Aplysia californica triggers a 30-min period of spontaneous firing termed the afterdischarge. Measurement of free calcium ion concentrations using calcium-sensitive electrodes revealed a biphasic pattern of elevation of intracellular calcium levels during the afterdischarge. Basal calcium levels at the soma were found to rise rapidly during afferent stimulation and then to decline before the onset of spontaneous firing. This early peak in intracellular calcium was followed by a slower, transient elevation of calcium levels during the period of rapid firing that occurs in the first few minutes of afterdischarge. Stimulation of clusters of bag cell neurons in a calcium-free external medium failed to trigger afterdischarge and produced no changes in basal intracellular calcium levels. 2. When calcium ions in the external medium were replaced by barium ions, stimulation of clusters of bag cell neurons triggered afterdischarges that were characterized by long-duration action potentials. Intracellular calcium levels during these afterdischarges rose slowly over the first few minutes of spontaneous firing. Because calcium-sensitive microelectrodes do not respond to barium ions, these data suggest that stimulation of afterdischarge triggers calcium release from an intracellular compartment. 3. During afterdischarges in barium-containing external media, each broadened action potential produced a discrete transient elevation of intracellular calcium levels. A similar effect was observed in isolated bag cell neurons in primary culture when action potentials were stimulated by depolarizing current pulses in a barium-containing medium. These data suggest that, under these conditions, individual action potentials trigger the release of intracellular calcium from some intracellular pool.
23
Zbicz, K. L., and F. F. Weight. "Transient voltage and calcium-dependent outward currents in hippocampal CA3 pyramidal neurons." Journal of Neurophysiology 53, no. 4 (April 1, 1985): 1038–58. http://dx.doi.org/10.1152/jn.1985.53.4.1038.
Full textAbstract:
Membrane currents activated by step changes in membrane potential were studied in hippocampal pyramidal neurons of region CA3 using the single microelectrode voltage-clamp technique. The transient outward current activated by depolarizing steps appeared to be composed of two transient currents that could be distinguished by differences in voltage sensitivity, time course, and pharmacological sensitivity. The more slowly decaying current was activated by voltage steps positive to -60 mV and declined exponentially with a time constant between 200 and 400 ms. This current inactivated as the holding potential was made more positive over the range of -75 to -45 mV and was 50% inactivated near -60 mV. The more slowly decaying transient current was selectively blocked by 0.5 mM 4-aminopyridine (4-AP) but not by 5-10 mM tetraethylammonium (TEA) or 2-5 mM Mn2+. The second transient current had a much faster time course than the 4-AP-sensitive current, having a duration of 5-20 ms. This very fast transient current was observed during potential steps positive to -45 mV. The fast transient current was inactivated when the holding potential was made positive to -45 mV. The amplitude of the fast transient current was greatly reduced by the application of 4 mM Mn2+ or Ca2+-free artificial cerebrospinal fluid (CSF). The fast transient current appeared to be unaffected by 0.5 mM 4-AP but was greatly reduced by 10 mM TEA. These results suggest that the transient outward current observed during depolarizing steps is composed of at least two distinct transient currents. The more slowly decaying current resembles the A-current originally described in molluscan neurons (9, 32, 42) in voltage sensitivity, time course, and pharmacological sensitivity. The faster transient current resembles a fast, Ca2+-dependent transient current previously observed in bull-frog sympathetic neurons (5, 27).
24
Pioner, Josè Manuel, Lorenzo Santini, Chiara Palandri, Daniele Martella, Flavia Lupi, Marianna Langione, Silvia Querceto, et al. "Optical Investigation of Action Potential and Calcium Handling Maturation of hiPSC-Cardiomyocytes on Biomimetic Substrates." International Journal of Molecular Sciences 20, no. 15 (August 3, 2019): 3799. http://dx.doi.org/10.3390/ijms20153799.
Full textAbstract:
Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are the most promising human source with preserved genetic background of healthy individuals or patients. This study aimed to establish a systematic procedure for exploring development of hiPSC-CM functional output to predict genetic cardiomyopathy outcomes and identify molecular targets for therapy. Biomimetic substrates with microtopography and physiological stiffness can overcome the immaturity of hiPSC-CM function. We have developed a custom-made apparatus for simultaneous optical measurements of hiPSC-CM action potential and calcium transients to correlate these parameters at specific time points (day 60, 75 and 90 post differentiation) and under inotropic interventions. In later-stages, single hiPSC-CMs revealed prolonged action potential duration, increased calcium transient amplitude and shorter duration that closely resembled those of human adult cardiomyocytes from fresh ventricular tissue of patients. Thus, the major contribution of sarcoplasmic reticulum and positive inotropic response to β-adrenergic stimulation are time-dependent events underlying excitation contraction coupling (ECC) maturation of hiPSC-CM; biomimetic substrates can promote calcium-handling regulation towards adult-like kinetics. Simultaneous optical recordings of long-term cultured hiPSC-CMs on biomimetic substrates favor high-throughput electrophysiological analysis aimed at testing (mechanistic hypothesis on) disease progression and pharmacological interventions in patient-derived hiPSC-CMs.
25
Thompson, S. M., and D. A. Prince. "Activation of electrogenic sodium pump in hippocampal CA1 neurons following glutamate-induced depolarization." Journal of Neurophysiology 56, no. 2 (August 1, 1986): 507–22. http://dx.doi.org/10.1152/jn.1986.56.2.507.
Full textAbstract:
Intracellular recordings were obtained from guinea pig hippocampal CA1 pyramidal neurons maintained in vitro. Focal applications of glutamate produced depolarizations followed by prolonged hyperpolarizations. The mechanisms underlying this postglutamate hyperpolarization (PGH) were investigated. PGH did not reverse polarity with hyperpolarization to potentials at or near the presumed K+ equilibrium potential. A transient increase in conductance was associated with the PGH; control values returned well before the termination of PGH. Application of Mn2+, an antagonist of voltage-dependent calcium conductance, blocked synaptic transmission and the afterhyperpolarization (AHP) that follows a directly evoked train of action potentials but did not diminish the PGH or the transient conductance increase. Intracellular application of the calcium chelator ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid blocked AHP but did not affect PGH. Reductions in temperature from 37 to 27-32 degrees C reduced the amplitude of PGH and prolonged its duration but increased the amplitude and duration of AHP. The transient conductance increase associated with PGH was unaffected. Application of strophanthidin, a specific antagonist of Na+-K+-ATPase, reversibly blocked PGH and led to large increases in the amplitude and duration of the AHP. It is concluded that PGH is produced by activation of the electrogenic sodium pump by glutamate-induced excitation. As such, PGH is a useful physiological assay of electrogenic sodium transport. In addition, maintenance of the Na+ gradient by the sodium pump is important for the buffering of Ca2+ influx.
26
Paudel, Roshan, Mohsin Saleet Jafri, and Aman Ullah. "The Role of Ca2+ Sparks in Force Frequency Relationships in Guinea Pig Ventricular Myocytes." Biomolecules 12, no. 11 (October 27, 2022): 1577. http://dx.doi.org/10.3390/biom12111577.
Full textAbstract:
Calcium sparks are the elementary Ca2+ release events in excitation-contraction coupling that underlie the Ca2+ transient. The frequency-dependent contractile force generated by cardiac myocytes depends upon the characteristics of the Ca2+ transients. A stochastic computational local control model of a guinea pig ventricular cardiomyocyte was developed, to gain insight into mechanisms of force-frequency relationship (FFR). This required the creation of a new three-state RyR2 model that reproduced the adaptive behavior of RyR2, in which the RyR2 channels transition into a different state when exposed to prolonged elevated subspace [Ca2+]. The model simulations agree with previous experimental and modeling studies on interval-force relations. Unlike previous common pool models, this local control model displayed stable action potential trains at 7 Hz. The duration and the amplitude of the [Ca2+]myo transients increase in pacing rates consistent with the experiments. The [Ca2+]myo transient reaches its peak value at 4 Hz and decreases afterward, consistent with experimental force-frequency curves. The model predicts, in agreement with previous modeling studies of Jafri and co-workers, diastolic sarcoplasmic reticulum, [Ca2+]sr, and RyR2 adaptation increase with the increased stimulation frequency, producing rising, rather than falling, amplitude of the myoplasmic [Ca2+] transients. However, the local control model also suggests that the reduction of the L-type Ca2+ current, with an increase in pacing frequency due to Ca2+-dependent inactivation, also plays a role in the negative slope of the FFR. In the simulations, the peak Ca2+ transient in the FFR correlated with the highest numbers of SR Ca2+ sparks: the larger average amplitudes of those sparks, and the longer duration of the Ca2+ sparks.
27
Chen, Y., X. D. Sun, and S. Herness. "Characteristics of action potentials and their underlying outward currents in rat taste receptor cells." Journal of Neurophysiology 75, no. 2 (February 1, 1996): 820–31. http://dx.doi.org/10.1152/jn.1996.75.2.820.
Full textAbstract:
1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.
28
Lin, Eric, Calvin Craig, Marcel Lamothe, Marinko V. Sarunic, Mirza Faisal Beg, and Glen F. Tibbits. "Construction and use of a zebrafish heart voltage and calcium optical mapping system, with integrated electrocardiogram and programmable electrical stimulation." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 308, no. 9 (May 1, 2015): R755—R768. http://dx.doi.org/10.1152/ajpregu.00001.2015.
Full textAbstract:
Zebrafish are increasingly being used as a model of vertebrate cardiology due to mammalian-like cardiac properties in many respects. The size and fecundity of zebrafish make them suitable for large-scale genetic and pharmacological screening. In larger mammalian hearts, optical mapping is often used to investigate the interplay between voltage and calcium dynamics and to investigate their respective roles in arrhythmogenesis. This report outlines the construction of an optical mapping system for use with zebrafish hearts, using the voltage-sensitive dye RH 237 and the calcium indicator dye Rhod-2 using two industrial-level CCD cameras. With the use of economical cameras and a common 532-nm diode laser for excitation, the rate dependence of voltage and calcium dynamics within the atrial and ventricular compartments can be simultaneously determined. At 140 beats/min, the atrial action potential duration was 36 ms and the transient duration was 53 ms. With the use of a programmable electrical stimulator, a shallow rate dependence of 3 and 4 ms per 100 beats/min was observed, respectively. In the ventricle the action potential duration was 109 ms and the transient duration was 124 ms, with a steeper rate dependence of 12 and 16 ms per 100 beats/min. Synchronous electrocardiograms and optical mapping recordings were recorded, in which the P-wave aligns with the atrial voltage peak and R-wave aligns with the ventricular peak. A simple optical pathway and imaging chamber are detailed along with schematics for the in-house construction of the electrocardiogram amplifier and electrical stimulator. Laboratory procedures necessary for zebrafish heart isolation, cannulation, and loading are also presented.
29
ten Tusscher, K. H. W. J., D. Noble, P. J. Noble, and A. V. Panfilov. "A model for human ventricular tissue." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 4 (April 2004): H1573—H1589. http://dx.doi.org/10.1152/ajpheart.00794.2003.
Full textAbstract:
The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.
30
Frasier, Chad R., Jacy L. Wagnon, Yangyang Oliver Bao, Luke G. McVeigh, Luis F. Lopez-Santiago, Miriam H. Meisler, and Lori L. Isom. "Cardiac arrhythmia in a mouse model of sodium channel SCN8A epileptic encephalopathy." Proceedings of the National Academy of Sciences 113, no. 45 (October 26, 2016): 12838–43. http://dx.doi.org/10.1073/pnas.1612746113.
Full textAbstract:
Patients with early infantile epileptic encephalopathy (EIEE) are at increased risk for sudden unexpected death in epilepsy (SUDEP). De novo mutations of the sodium channel gene SCN8A, encoding the sodium channel Nav1.6, result in EIEE13 (OMIM 614558), which has a 10% risk of SUDEP. Here, we investigated the cardiac phenotype of a mouse model expressing the gain of function EIEE13 patient mutation p.Asn1768Asp in Scn8a (Nav1.6-N1768D). We tested Scn8aN1768D/+ mice for alterations in cardiac excitability. We observed prolongation of the early stages of action potential (AP) repolarization in mutant myocytes vs. controls. Scn8aN1768D/+ myocytes were hyperexcitable, with a lowered threshold for AP firing, increased incidence of delayed afterdepolarizations, increased calcium transient duration, increased incidence of diastolic calcium release, and ectopic contractility. Calcium transient duration and diastolic calcium release in the mutant myocytes were tetrodotoxin-sensitive. A selective inhibitor of reverse mode Na/Ca exchange blocked the increased incidence of diastolic calcium release in mutant cells. Scn8aN1768D/+ mice exhibited bradycardia compared with controls. This difference in heart rate dissipated after administration of norepinephrine, and there were no differences in heart rate in denervated ex vivo hearts, implicating parasympathetic hyperexcitability in the Scn8aN1768D/+ animals. When challenged with norepinephrine and caffeine to simulate a catecholaminergic surge, Scn8aN1768D/+ mice showed ventricular arrhythmias. Two of three mutant mice under continuous ECG telemetry recording experienced death, with severe bradycardia preceding asystole. Thus, in addition to central neuron hyperexcitability, Scn8aN1768D/+ mice have cardiac myoycte and parasympathetic neuron hyperexcitability. Simultaneous dysfunction in these systems may contribute to SUDEP associated with mutations of Scn8a.
31
Saegusa, Noriko, Vivek Garg, and Kenneth W. Spitzer. "Modulation of ventricular transient outward K+ current by acidosis and its effects on excitation-contraction coupling." American Journal of Physiology-Heart and Circulatory Physiology 304, no. 12 (June 15, 2013): H1680—H1696. http://dx.doi.org/10.1152/ajpheart.00070.2013.
Full textAbstract:
The contribution of transient outward current ( Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved, as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current ( ICa,L), and calcium transients (CaTs) in rabbit ventricular myocytes. Intracellular acidosis [pHi 6.75 with extracellular pH (pHo) 7.4] reduced Ito by ∼50% in myocytes with both high (epicardial) and low (papillary muscle) Ito densities, with little effect on steady-state inactivation and activation. Of the two candidate α-subunits underlying Ito, human (h)Kv4.3 and hKv1.4, only hKv4.3 current was reduced by intracellular acidosis. Extracellular acidosis (pHo 6.5) shifted Ito inactivation toward less negative potentials but had negligible effect on peak current at +60 mV when initiated from −80 mV. The effects of low pHi-induced inhibition of Ito on AP repolarization were much greater in epicardial than papillary muscle myocytes and included slowing of phase 1, attenuation of the notch, and elevation of the plateau. Low pHi increased AP duration in both cell types, with the greatest lengthening occurring in epicardial myocytes. The changes in epicardial AP repolarization induced by intracellular acidosis reduced peak ICa,L, increased net calcium influx via ICa,L, and increased CaT amplitude. In summary, in contrast to low pHo, intracellular acidosis has a marked inhibitory effect on ventricular Ito, perhaps mediated by Kv4.3. By altering the trajectory of the AP repolarization, low pHi has a significant indirect effect on calcium handling, especially evident in epicardial cells.
32
Hayashi, H., T. Watanabe, and T. F. McDonald. "Action potential duration in ventricular muscle during selective metabolic block." American Journal of Physiology-Heart and Circulatory Physiology 253, no. 2 (August 1, 1987): H373—H379. http://dx.doi.org/10.1152/ajpheart.1987.253.2.h373.
Full textAbstract:
We have examined whether maintenance of the cardiac action potential duration depends exclusively on energy from glycolysis. Oxidative phosphorylation in guinea pig papillary muscles was inhibited by superfusion with hypoxic solutions. After 60 min in 50 mM glucose solution, the action potential duration was 85% of aerobic control, but ATP content was only 25%; after 60 min in 0 mM glucose, both the duration and ATP content had declined to 15% control. When the glucose concentration of hypoxic solution was raised from 0 to 50 mM, there was nearly full recovery of the action potential duration but ATP only increased to about 25% control. We attribute action potential shortening during metabolic inhibition to suppression of calcium current and activation of potassium current; the latter are graded in intensity and expressed only at low ATP. When normoxic muscle was treated with 20 mM 2-deoxy-D-glucose (2-DG) to inhibit glycolysis, there was an early transient shortening of the action potential. This was attributed to ATP consumption related to early rapid 2-DG influx and phosphorylation. After the transient, the action potential duration was maintained for several hours in oxygenated 2-DG solution. The duration was also maintained in oxygenated muscle depleted of glycolytic substrate. Thus we found no evidence of an exclusive relation between action potential duration and glycolysis.
33
Ruiz-Petrich, Elena, and Normand Leblanc. "The mechanism of the rate-dependent changes of the conducted action potential in rabbit ventricle." Canadian Journal of Physiology and Pharmacology 67, no. 7 (July 1, 1989): 780–87. http://dx.doi.org/10.1139/y89-124.
Full textAbstract:
Blockers of the transient outward current (4-aminopyridine) and the Ca current (Co2+) as well as injection of polarizing current during the plateau were used to assess the role of these current systems as determinants of action potential duration at different pacing rates. Papillary muscles and ventricular trabecula were superfused with oxygenated Krebs solution at 33 °C and driven at a basic rate of 1 Hz. The effects of varying the frequency of stimulation between 0.1 and 4 Hz on action potential parameters were determined under control conditions and during exposure to 2 mM 4-aminopyridine, 1–3 mM CoCl2, or a mixture of 4-aminopyridine and CoCl2. The control relationship between action potential duration and pacing rate showed a maximum between 1 and 2 Hz. Under 4-aminopyridine, the plateau height and the action potential duration increased. The rate-dependent shortening of the action potential at frequencies below 1 Hz was reduced or abolished, and enhanced shortening was observed at rates above 1 Hz. Exposure to Co2+ reduced the action potential shortening at rates higher than 1 Hz. Both blockers, 4-aminopyridine and Co2+ were necessary to eliminate the rate-dependent changes of the action potential duration. Our results indicated that both the transient outward current and the inward calcium current determine the plateau height and duration for frequencies ≤2 Hz, whereas at higher rates, the Ca current plays a dominant role.Key words: action potential duration, stimulation rate, Ca current, transient outward current.
34
Livshitz, Leonid, Keith Decker, Gregory Faber, Thomas O'Hara, Jonathan Silva, and Yoram Rudy. "Comments on “A model for human ventricular tissue”." American Journal of Physiology-Heart and Circulatory Physiology 288, no. 1 (January 2005): H453. http://dx.doi.org/10.1152/ajpheart.00826.2004.
Full textAbstract:
The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue. Comments on “A model for human ventricular tissue” by K. H. W. J. ten Tusscher et al.
35
Martins, Eduardo, Kenji Inamura, Klas Themner, Klas G. Malmqvist, and Bo K. Siesjö. "Accumulation of Calcium and Loss of Potassium in the Hippocampus following Transient Cerebral Ischemia: A Proton Microprobe Study." Journal of Cerebral Blood Flow & Metabolism 8, no. 4 (August 1988): 531–38. http://dx.doi.org/10.1038/jcbfm.1988.93.
Full textAbstract:
This study explored (a) whether postischemic accumulation of calcium in hippocampal neurons precedes or occurs pari passu with light microscopical signs of delayed neuronal necrosis, and (b) whether calcium initially accumulates in dendritic domains, presumed to have a high density of agonist-operated calcium channels. Transient ischemia of 10-min duration was induced in rats, and the animals were studied after 1, 2, 3, and 4 days of recovery. We measured total calcium and potassium contents in the stratum oriens, pyramidale, radiatum, and moleculare of the CA1 and CA3 sectors, using particle induced x-ray emission (PIXE) in the proton microprobe mode. The results showed significant accumulation of calcium and loss of potassium after 3 and 4 days of recovery in the CA1 sector, which developed neuronal necrosis, but not in the CA3 sector, which showed only occasional damage. In a few animals, calcium accumulation (and loss of potassium) was observed with no or only mild visible damage, but in the majority of animals the accumulation of calcium correlated to signs of neuronal necrosis. Since calcium accumulation was similar in all strata examined, the results failed to reveal preferential accumulation in dendritic or somal regions. Based on our results and those of Dux et al., we emphasize the possibility that delayed neuronal death is, at least in part, caused by increased calcium cycling of plasma membranes and gradual calcium overload of mitochondria.
36
Nguyen, My-Hanh T., S. J. Dudycha, and M. Saleet Jafri. "Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics." American Journal of Physiology-Cell Physiology 292, no. 6 (June 2007): C2004—C2020. http://dx.doi.org/10.1152/ajpcell.00271.2006.
Full textAbstract:
The energy production of mitochondria in heart increases during exercise. Several works have suggested that calcium acts at multiple control points to activate net ATP production in what is termed “parallel activation”. To study this, a computational model of mitochondrial energy metabolism in the heart has been developed that integrates the Dudycha-Jafri model for the tricarboxylic acid cycle with the Magnus-Keizer model for mitochondrial energy metabolism and calcium dynamics. The model improves upon the previous formulation by including an updated formulation for calcium dynamics, and new descriptions of sodium, hydrogen, phosphate, and ATP balance. To this end, it incorporates new formulations for the calcium uniporter, sodium-calcium exchange, sodium-hydrogen exchange, the F1F0-ATPase, and potassium-hydrogen exchange. The model simulates a wide range of experimental data, including steady-state and simulated pacing protocols. The model suggests that calcium is a potent activator of net ATP production and that as pacing increases energy production due to calcium goes up almost linearly. Furthermore, it suggests that during an extramitochondrial calcium transient, calcium entry and extrusion cause a transient depolarization that serve to increase NADH production by the tricarboxylic acid cycle and NADH consumption by the respiration driven proton pumps. The model suggests that activation of the F1F0-ATPase by calcium is essential to increase ATP production. In mitochondria very close to the release sites, the depolarization is more severe causing a temporary loss of ATP production. However, due to the short duration of the depolarization the net ATP production is also increased.
37
Hilgemann, D. W. "Extracellular calcium transients at single excitations in rabbit atrium measured with tetramethylmurexide." Journal of General Physiology 87, no. 5 (May 1, 1986): 707–35. http://dx.doi.org/10.1085/jgp.87.5.707.
Full textAbstract:
Extracellular calcium transients were resolved within the time course of single contraction cycles in rabbit left atrium using tetramethylmurexide (2 mM) as the calcium-sensitive dye (150-250 microM total calcium, 80-150 microM free calcium). Net extracellular calcium depletion began within 2-4 ms upon excitation; over the following 5-20 ms, depletion continued steeply and amounted to 0.2 mumol/kg wet weight X 10 ms (135 microM free extracellular calcium). In regularly excited muscles (0.5-2 Hz), net depletion slowed rapidly and stopped early during the rise of contractile motion monitored by transmitted light. Maximum depletions amounted to 0.2-0.5% of total extracellular calcium (0.2-0.5 mumol/kg wet weight with 135 microM free calcium). Replenishment of extracellular calcium began at the latest midway to the peak of the motion signal. Calcium replenishment could be complete for the most part by an early phase of relaxation or could take place continuously through relaxation. The maximal net depletion per beat decreased manyfold with a decrease of frequency from 1 to 0.05 Hz. During paired pulse stimulation (200-300-ms twin pulse separation at basal rates of 0.3-1 Hz), extracellular calcium accumulation was enhanced at the initial potentiated contraction; extracellular calcium depletion was prolonged at the low-level premature contraction. With quadruple stimulation (three premature excitations), the apparent rate of net extracellular calcium accumulation at potentiated contractions approached or exceeded the apparent rate of early net calcium depletion. Under the special circumstance of a strongly potentiated post-stimulatory contraction after greater than 5 s rest, repolarization beyond -40 mV occurred within 10 ms, net extracellular calcium accumulation began with the onset of muscle motion, and net extracellular calcium accumulation (1-3 microM/kg wet weight) coincided with a more positive late action potential in comparison with subsequent action potentials. Consistent changes of the apparent rate of early net calcium depletion were not found with any of the simulation patterns examined. In ryanodine-pretreated atria, the duration of depletion was clearly limited by action potential duration at post-rest stimulations; in the presence of 4-aminopyridine (2 mM), depletion continued essentially undiminished for up to 200 ms. The resulting net depletion magnitudes were greater than 10 times larger than the transient depletions found during steady stimulation.
38
Zaniboni, Massimiliano. "Ventricular Repolarization and Calcium Transient Show Resonant Behavior under Oscillatory Pacing Rate." Biomolecules 12, no. 7 (June 23, 2022): 873. http://dx.doi.org/10.3390/biom12070873.
Full textAbstract:
Cardiac EC coupling is triggered by rhythmic depolarizing current fronts originating from the sino-atrial node, and the way variability in rhythm is associated with variability in action potential duration (APD) and, in turn, in the variability of calcium transient amplitude (CTA) and contraction is a key determinant of beating stability. Sinusoidal-varying pacing rate is adopted here in order to establish whether APD and CTA oscillations, elicited in a human ventricular AP model (OR) under oscillatory pacing, are consistent with the dynamics of two coupled harmonic oscillators, e.g., a two-degree-of-freedom system of mass and springs (MS model). I show evidence that this is the case, and that the MS model, preliminarily fitted to OR behavior, retains key features of the physiological system, such as the dependence of APD and CTA oscillation amplitudes from average value and from beat-to-beat changes in pacing rate, and the phase relationship between them. The bi-directionality of coupling between APD and CTA makes it difficult to discriminate which one leads EC coupling dynamics under variable pacing. The MS model suggests that the calcium cycling, with its greater inertia chiefly determined by the SR calcium release, is the leading mechanism. I propose the present approach to also be relevant at the whole organ level, where the need of compact representations of electromechanical interaction, particularly in clinical practice, remains urgent.
39
Blackwell, K. T. "Calcium Waves and Closure of Potassium Channels in Response to GABA Stimulation in Hermissenda Type B Photoreceptors." Journal of Neurophysiology 87, no. 2 (February 1, 2002): 776–92. http://dx.doi.org/10.1152/jn.00867.2000.
Full textAbstract:
Classical conditioning of Hermissenda crassicornisrequires the paired presentation of a conditioned stimulus (light) and an unconditioned stimulus (turbulence). Light stimulation of photoreceptors leads to production of diacylglycerol, an activator of protein kinase C, and inositol triphosphate (IP3), which releases calcium from intracellular stores. Turbulence causes hair cells to release GABA onto the terminal branches of the type B photoreceptor. One prior study has shown that GABA stimulation produces a wave of calcium that propagates from the terminal branches to the soma and raises the possibility that two sources of calcium are required for memory storage. GABA stimulation also causes an inhibitory postsynaptic potential (IPSP) followed by a late depolarization and increase in input resistance, whose cause has not been identified. A model was developed of the effect of GABA stimulation on the Hermissenda type B photoreceptor to evaluate the currents underlying the late depolarization and to evaluate whether a calcium wave could propagate from the terminal branches to the soma. The model included GABAA, GABAB, and calcium-sensitive potassium leak channels; calcium dynamics including release of calcium from intracellular stores; and the biochemical reactions leading from GABAB receptor activation to IP3 production. Simulations show that it is possible for a wave of calcium to propagate from the terminal branches to the soma. The wave is initiated by IP3-induced calcium release but propagation requires release through the ryanodine receptor channel where IP3 concentration is small. Wave speed is proportional to peak calcium concentration at the crest of the wave, with a minimum speed of 9 μm/s in the absence of IP3. Propagation ceases when peak concentration drops below 1.2 μM; this occurs if the rate of calcium pumping into the endoplasmic reticulum is too large. Simulations also show that both a late depolarization and an increase in input resistance occur after GABA stimulation. The duration of the late depolarization corresponds to the duration of potassium leak channel closure. Neither the late depolarization nor the increase in input resistance are observed when a transient calcium current and a hyperpolarization-activated current are added to the model as replacement for closure of potassium leak channels. Thus the late depolarization and input resistance elevation can be explained by a closure of calcium-sensitive leak potassium currents but cannot be explained by a transient calcium current and a hyperpolarization-activated current.
40
Klos, Matthew L., Wanqing Hou, Bernard Nsengimana, Shiwang Weng, Chuyun Yan, Suowen Xu, Eric Devaney, and Shuxin Han. "Differential Effects of Beta-Hydroxybutyrate Enantiomers on Induced Pluripotent Stem Derived Cardiac Myocyte Electrophysiology." Biomolecules 12, no. 10 (October 17, 2022): 1500. http://dx.doi.org/10.3390/biom12101500.
Full textAbstract:
Beta-hydroxybutyrate (βOHB), along with acetoacetate and acetone, are liver-produced ketone bodies that are increased after fasting or prolonged exercise as an alternative fuel source to glucose. βOHB, as the main circulating ketone body, is not only a G-protein coupled receptor ligand but also a histone deacetylases inhibitor, prompting the reexamination of its role in health and disease. In this study, we compared the effects of two commercial βOHB formulations an enantiomer R βOHB and a racemic mixture ± βOHB on induced pluripotent stem cell cardiac myocytes (iPS-CMs) electrophysiology. Cardiac myocytes were cultured in R βOHB or ± βOHB for at least ten days after lactate selection. Flouvolt or Fluo-4 was used to assay iPS-CMs electrophysiology. We found that while both formulations increased the optical potential amplitude, R βOHB prolonged the action potential duration but ± βOHB shortened the action potential duration. Moreover, ± βOHB increased the peak calcium transient but R βOHB reduced the peak calcium transient. Co-culturing with glucose or fatty acids did not ameliorate the effects, suggesting that βOHB was more than a fuel source. The effect of βOHB on iPS-CMs electrophysiology is most likely stereoselective, and care must be taken to evaluate the role of exogenous βOHB in health and disease.
41
Ma, Jiying, and Dongmei Xiao. "Nonlinear dynamics of a mathematical model on action potential duration and calcium transient in paced cardiac cells." Discrete & Continuous Dynamical Systems - B 18, no. 9 (2013): 2377–96. http://dx.doi.org/10.3934/dcdsb.2013.18.2377.
Full text
42
Srivastava, Shekhar, Leon Collis, Anita Go, Salvatore Mancarella, William A. Coetzee, and Michael Artman. "Paradoxical Effect of Dofetilide on Action Potential Duration and Calcium Transient Amplitude in Newborn Rabbit Ventricular Myocytes." Journal of Cardiovascular Pharmacology 45, no. 2 (February 2005): 165–74. http://dx.doi.org/10.1097/01.fjc.0000151896.57637.66.
Full text
43
Greenstein, Joseph L., Richard Wu, Sunny Po, Gordon F. Tomaselli, and Raimond L. Winslow. "Role of the Calcium-Independent Transient Outward Current I to1 in Shaping Action Potential Morphology and Duration." Circulation Research 87, no. 11 (November 24, 2000): 1026–33. http://dx.doi.org/10.1161/01.res.87.11.1026.
Full text
44
Lee, Hsiang-Chun, Chi Wei, Liang-Yin Ke, Pei-Shang Tsai, Hsin-Ting Lin, Yi-Lin Shiao, Bin-Nan Wu, Chu-Huang Chen, and Sheng-Hsiung Sheu. "Atherogenic Very-Low-Density Lipoprotein Shortens Atrial Action Potential Duration by Increasing Potassium Currents and Calcium Transient." Biophysical Journal 108, no. 2 (January 2015): 586a. http://dx.doi.org/10.1016/j.bpj.2014.11.3196.
Full text
45
Lacombe, Véronique A., Serge Viatchenko-Karpinski, Dmitry Terentyev, Arun Sridhar, Sitaramesh Emani, John D. Bonagura, David S. Feldman, Sandor Györke, and Cynthia A. Carnes. "Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 293, no. 5 (November 2007): R1787—R1797. http://dx.doi.org/10.1152/ajpregu.00059.2007.
Full textAbstract:
Isolated diastolic dysfunction is found in almost half of asymptomatic patients with well-controlled diabetes and may precede diastolic heart failure. However, mechanisms that underlie diastolic dysfunction during diabetes are not well understood. We tested the hypothesis that isolated diastolic dysfunction is associated with impaired myocardial Ca2+ handling during type 1 diabetes. Streptozotocin-induced diabetic rats were compared with age-matched placebo-treated rats. Global left ventricular myocardial performance and systolic function were preserved in diabetic animals. Diabetes-induced diastolic dysfunction was evident on Doppler flow imaging, based on the altered patterns of mitral inflow and pulmonary venous flows. In isolated ventricular myocytes, diabetes resulted in significant prolongation of action potential duration compared with controls, with afterdepolarizations occurring in diabetic myocytes ( P < 0.05). Sustained outward K+ current and peak outward component of the inward rectifier were reduced in diabetic myocytes, while transient outward current was increased. There was no significant change in L-type Ca2+ current; however, Ca2+ transient amplitude was reduced and transient decay was prolonged by 38% in diabetic compared with control myocytes ( P < 0.05). Sarcoplasmic reticulum Ca2+ load (estimated by measuring the integral of caffeine-evoked Na+-Ca2+ exchanger current and Ca2+ transient amplitudes) was reduced by ∼50% in diabetic myocytes ( P < 0.05). In permeabilized myocytes, Ca2+ spark amplitude and frequency were reduced by 34 and 20%, respectively, in diabetic compared with control myocytes ( P < 0.05). Sarco(endo)plasmic reticulum Ca2+-ATPase-2a protein levels were decreased during diabetes. These data suggest that in vitro impairment of Ca2+ reuptake during myocyte relaxation contributes to in vivo diastolic dysfunction, with preserved global systolic function, during diabetes.
46
Payne, Richard J., Marc A. Tewfik, Michael P. Hier, Michael Tamilia, Elizabeth Mac Namara, Jonathan Young, and Martin J. Black. "Benefits Resulting from 1-and 6-Hour Parathyroid Hormone and Calcium Levels After Thyroidectomy." Otolaryngology–Head and Neck Surgery 133, no. 3 (September 2005): 386–90. http://dx.doi.org/10.1016/j.otohns.2005.02.021.
Full textAbstract:
OBJECTIVE: Previous studies have established the efficacy of post-thyroidectomy hypocalcemia monitoring using parathyroid hormone (PTH) and corrected calcium levels at 1 and 6 hours. The goal of this study was to measure the impact of managing patients based on the above findings with respect to: duration of hospital stays, rates of transient hypocalcemia, number of blood tests, cost savings, and discharge from the hospital as early as 8 hours post-thyroidectomy without compromising safety. STUDY DESIGN AND SETTING: This is a prospective study involving 95 total thyroidectomy patients using historical data as controls. The previous protocol was modified in that all blood tests ceased for patients meeting the 6-hour critical level of PTH ≥ 28 ng/L and simultaneous corrected calcium ≥ 2.14 mmol/L (8.56 mg/dL). Furthermore, patients with 1-hour PTH levels ≤ 8 ng/L were prophylactically treated with calcium and vitamin D supplementation. RESULTS: This study demonstrates lower rates of transient hypocalcemia from 28% to 9% (OR = 4.13, P = 0.016), a 10-hour reduction in mean hospital stay, and fewer blood tests (23 vs 15) for patients undergoing total thyroidectomy since the implementation of the new protocol. Furthermore, the experimental protocol resulted in an average cost savings of $766 per patient. CONCLUSIONS: The new algorithm resulting from PTH and corrected calcium monitoring at 1 and 6 hours post-thyroidectomy has led to significant cost savings for our institution. It has also translated into greater patient satisfaction as a result of fewer blood tests, a lower incidence of transient hypocalcemia, and significantly shorter hospital stays.
47
Nashat, Amir H., and Robert Langer. "Temporal Characteristics of Activation, Deactivation, and Restimulation of Signal Transduction following Depolarization in the Pheochromocytoma Cell Line PC12." Molecular and Cellular Biology 23, no. 14 (July 15, 2003): 4788–95. http://dx.doi.org/10.1128/mcb.23.14.4788-4795.2003.
Full textAbstract:
ABSTRACT This study focuses on the transient and dynamic activation of intracellular signal transduction following different protocols of depolarization. During chronic depolarization, phosphorylation of extracellular signal-regulated kinases (ERKs) was observed to peak and subsequently fall to low levels within 10 min of depolarization. Short periods of depolarization, from 1 to 5 min in duration, also led to phosphorylation of ERK, and the rate of ERK dephosphorylation was not affected by the duration of depolarization. Phosphorylation of the cyclic AMP response element binding protein (CREB) also peaked as a result of chronic depolarization but decreased to intermediate levels that were maintained for more than 1 h. Pulsatile depolarization was explored as a means to circumvent the deactivation of intracellular signaling activity during chronic depolarization. Both ERK and CREB were rephosphorylated by a second period of depolarization that followed a recovery period of 10 min or more. The effects of the durations of depolarization and interpulse recovery on reactivation of ERK and CREB were characterized. Measurements of free cytoplasmic Ca2+ confirmed the transient rise in the intracellular calcium concentration ([Ca2+]i) during chronic depolarization and the pulsatile increase in [Ca2+]i that can be achieved with short periods of depolarization. This study characterizes the dynamic activities of signal transduction following depolarization. Electrical stimulation of neurons induces many cellular changes that unfold over time, and the influx of Ca2+ ions that mediate these events is transient. This study suggests that pulsatile activity may be a means of maintaining signaling activity over long periods of time.
48
Munzenmaier, D. H., and A. S. Greene. "Angiotensin II mediates a sustained rise in nuclear and cytoplasmic calcium via multiple receptor subtypes." American Journal of Physiology-Heart and Circulatory Physiology 269, no. 2 (August 1, 1995): H565—H570. http://dx.doi.org/10.1152/ajpheart.1995.269.2.h565.
Full textAbstract:
Alterations in nuclear calcium levels in response to angiotensin II (ANG II) may play an important role in the trophic actions of ANG II. This study utilized confocal microscopy and nuclear staining to test the hypothesis that both nuclear and cytoplasmic calcium levels are altered in response to ANG II stimulation of freshly dissociated aortic smooth muscle cells. Cells were loaded with the calcium indicator fluo 3 acetoxymethyl ester, and the calcium response to ANG II stimulation was analyzed over time with a laser-scanning confocal microscope. Additionally, the ratiometric calcium indicator fura 2 acetoxymethyl ester and conventional fluorescence microscopy were used to verify these observations. Results show that basal nuclear calcium exceeds cytoplasmic calcium in these cells. Stimulation by ANG II induces a sustained rise (separate from the rapid transient) in both nuclear and cytoplasmic calcium in excess of 20 min in duration. This rise was blockable by either the AT1 receptor antagonist DuP-753 or by the AT2 antagonist PD-123319. Thus ANG II stimulates a sustained rise in nuclear calcium by a mechanism that necessitates activation of both AT1 and AT2 receptors.
49
Hirose, R., and E. B. Chang. "Effects of serotonin on Na+-H+ exchange and intracellular calcium in isolated chicken enterocytes." American Journal of Physiology-Gastrointestinal and Liver Physiology 254, no. 6 (June 1, 1988): G891—G897. http://dx.doi.org/10.1152/ajpgi.1988.254.6.g891.
Full textAbstract:
The effects of serotonin or 5-hydroxytryptamine (5-HT) on Na absorption and intracellular free Ca (Cai) in isolated chicken enterocytes was examined. The rate of initial 22Na uptake was inhibited by 50% after 90 s of stimulation with 5-HT (10(-5) M), an effect that was not additive with amiloride (10(-3) M) and was transient (less than 10 min). 5-HT similarly decreased intracellular pH (pHi) in cells loaded with the pH indicator carboxyfluorescein, an effect that was also transient, not additive with amiloride, and Na dependent. The ED50 of this effect was approximately 10(-8) M. 5-HT also stimulated a transient increase in Cai as determined by quin2 fluorescence. A maximal increase of 60 nM occurred significantly before the peak change in pHi, but the total duration of response was similar in each case. In the absence of extracellular Ca, the 5-HT effects on pHi and Cai still persisted. In cells loaded with the Ca-buffering agent MAPTAM, the 5-HT (10(-5) M) inhibitory effect of 22Na influx was partially inhibited. We conclude that 5-HT directly inhibits Na absorption by isolated enterocytes by releasing endogenous Ca, which subsequently causes an inhibition of amiloride-sensitive Na+-H+ exchange.
50
Tsuchida, Katsuharu, and Hiroshi Watajima. "Potassium currents in ventricular myocytes from genetically diabetic rats." American Journal of Physiology-Endocrinology and Metabolism 273, no. 4 (October 1, 1997): E695—E700. http://dx.doi.org/10.1152/ajpendo.1997.273.4.e695.
Full textAbstract:
Our previous study demonstrated the longer duration of action potential in ventricular myocytes from genetically diabetic WBN/Kob rats without change in calcium channel density compared with age-matched controls [Tsuchida, K., H. Watajima, and S. Otamo. Am. J. Physiol. 267 ( Heart Circ. Physiol. 36): H2280–H2289, 1994]. In the present study we examined the alteration of potassium currents, especially transient outward current, in ventricular myocytes of genetically diabetic WBN/Kob rats. WBN/Kob rats gradually develop hyperglycemia with aging and show some similarity to non-insulin-dependent diabetes mellitus models, which differ from the insulin-dependent streptozotocin-treated rat model. The density of the intracellular calcium ion-independent transient outward current ( I to) from 17- to 19-mo diabetic rat myocytes was significantly smaller than that from age-matched control rat myocytes. In addition, the density of I to from 17- to 19-mo rat myocytes was significantly less than that from 2-mo rat myocytes, suggesting that aging-induced alteration of I to was accelerated by the diabetic state. The steady-state inactivation curves of I to, the recovery from I toinactivation, and the other outward currents were not significantly altered between diabetic myocytes and age-matched control myocytes. In conclusion, the prolonged duration of action potential from genetically diabetic rat myocytes is mainly due to the depressed I to.