Literatura científica selecionada sobre o tema "BKCa channels"
Crie uma referência precisa em APA, MLA, Chicago, Harvard, e outros estilos
Consulte a lista de atuais artigos, livros, teses, anais de congressos e outras fontes científicas relevantes para o tema "BKCa channels".
Ao lado de cada fonte na lista de referências, há um botão "Adicionar à bibliografia". Clique e geraremos automaticamente a citação bibliográfica do trabalho escolhido no estilo de citação de que você precisa: APA, MLA, Harvard, Chicago, Vancouver, etc.
Você também pode baixar o texto completo da publicação científica em formato .pdf e ler o resumo do trabalho online se estiver presente nos metadados.
Artigos de revistas sobre o assunto "BKCa channels"
1
Zhu, Shu, Darren D. Browning, Richard E. White, David Fulton e Scott A. Barman. "Mutation of protein kinase C phosphorylation site S1076 on α-subunits affects BKCa channel activity in HEK-293 cells". American Journal of Physiology-Lung Cellular and Molecular Physiology 297, n.º 4 (outubro de 2009): L758—L766. http://dx.doi.org/10.1152/ajplung.90518.2008.
Texto completo da fonteResumo:
Large conductance, calcium- and voltage-activated potassium (BKCa) channels are important modulators of pulmonary vascular smooth muscle membrane potential, and phosphorylation of BKCa channels by protein kinases regulates pulmonary arterial smooth muscle function. However, little is known about the effect of phosphorylating specific channel subunits on BKCa channel activity. The present study was done to determine the effect of mutating protein kinase C (PKC) phosphorylation site serine 1076 (S1076) on transfected human BKCa channel α-subunits in human embryonic kidney (HEK-293) cells, a heterologous expression system devoid of endogenous BKCa channels. Results showed that mutating S1076 altered the effect of PKC activation on BKCa channels in HEK-293 cells. Specifically, the phospho-deficient mutation BKCa-α(S1076A)/β1 attenuated the excitatory effect of the PKC activator phorbol myristate acetate (PMA) on BKCa channels, whereas the phospho-mimetic mutation BKCa-α(S1076E)/β1 increased the excitatory effect of PMA on BKCa channels. In addition, the phospho-null mutation S1076A blocked the activating effect of cGMP-dependent protein kinase G (PKG) on BKCa channels. Collectively, these results suggest that specific putative PKC phosphorylation site(s) on human BKCa channel α-subunits influences BKCa channel activity, which may subsequently alter pulmonary vascular smooth muscle function and tone.
2
Zhao, Guiling, Zachary P. Neeb, M. Dennis Leo, Judith Pachuau, Adebowale Adebiyi, Kunfu Ouyang, Ju Chen e Jonathan H. Jaggar. "Type 1 IP3 receptors activate BKCa channels via local molecular coupling in arterial smooth muscle cells". Journal of General Physiology 136, n.º 3 (16 de agosto de 2010): 283–91. http://dx.doi.org/10.1085/jgp.201010453.
Texto completo da fonteResumo:
Plasma membrane large-conductance Ca2+-activated K+ (BKCa) channels and sarcoplasmic reticulum inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are expressed in a wide variety of cell types, including arterial smooth muscle cells. Here, we studied BKCa channel regulation by IP3 and IP3Rs in rat and mouse cerebral artery smooth muscle cells. IP3 activated BKCa channels both in intact cells and in excised inside-out membrane patches. IP3 caused concentration-dependent BKCa channel activation with an apparent dissociation constant (Kd) of ∼4 µM at physiological voltage (−40 mV) and intracellular Ca2+ concentration ([Ca2+]i; 10 µM). IP3 also caused a leftward-shift in BKCa channel apparent Ca2+ sensitivity and reduced the Kd for free [Ca2+]i from ∼20 to 12 µM, but did not alter the slope or maximal Po. BAPTA, a fast Ca2+ buffer, or an elevation in extracellular Ca2+ concentration did not alter IP3-induced BKCa channel activation. Heparin, an IP3R inhibitor, and a monoclonal type 1 IP3R (IP3R1) antibody blocked IP3-induced BKCa channel activation. Adenophostin A, an IP3R agonist, also activated BKCa channels. IP3 activated BKCa channels in inside-out patches from wild-type (IP3R1+/+) mouse arterial smooth muscle cells, but had no effect on BKCa channels of IP3R1-deficient (IP3R1−/−) mice. Immunofluorescence resonance energy transfer microscopy indicated that IP3R1 is located in close spatial proximity to BKCa α subunits. The IP3R1 monoclonal antibody coimmunoprecipitated IP3R1 and BKCa channel α and β1 subunits from cerebral arteries. In summary, data indicate that IP3R1 activation elevates BKCa channel apparent Ca2+ sensitivity through local molecular coupling in arterial smooth muscle cells.
3
Xie, Man-Jiang, Yu-Guang Ma, Fang Gao, Yun-Gang Bai, Jiu-Hua Cheng, Yao-Ming Chang, Zhi-Bin Yu e Jin Ma. "Activation of BKCa channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats". American Journal of Physiology-Cell Physiology 298, n.º 6 (junho de 2010): C1489—C1500. http://dx.doi.org/10.1152/ajpcell.00474.2009.
Texto completo da fonteResumo:
Cerebral arterial remodeling is one of the critical factors in the occurrence of postspaceflight orthostatic intolerance. We hypothesize that large-conductance calcium-activated K+ (BKCa) channels in vascular smooth muscle cells (VSMCs) may play an important role in regulating cerebrovascular adaptation during microgravity exposure. The aim of this work was to investigate whether activation of BKCa channels is involved in regulation of apoptotic remodeling of cerebral arteries in simulated microgravity rats. In animal studies, Sprague-Dawley rats were subjected to 1-wk hindlimb unweighting to simulate microgravity. Alterations of BKCa channels in cerebral VSMCs were investigated by patch clamp and Western blotting; apoptosis was assessed by electron microscopy and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL). To evaluate the correlation of BKCa channel and apoptosis, channel protein and cell nucleus were double-stained. In cell studies, hSloα+β1 channel was coexpressed into human embryonic kidney 293 (HEK293) cells to observe the effects of BKCa channels on apoptosis. In rats, enhanced activities and expression of BKCa channels were found to be correlated with increased apoptosis in cerebral VSMCs after simulated microgravity. In transfected HEK293 cells, activation of cloned BKCa channel induced apoptosis, whereas inhibition of cloned BKCa channel decreased apoptosis. In conclusion, activation of BKCa channels is associated with increased apoptosis in cerebral VSMCs of simulated microgravity rats.
4
Ling, Shizhang, Jian-Zhong Sheng e Andrew P. Braun. "The calcium-dependent activity of large-conductance, calcium-activated K+ channels is enhanced by Pyk2- and Hck-induced tyrosine phosphorylation". American Journal of Physiology-Cell Physiology 287, n.º 3 (setembro de 2004): C698—C706. http://dx.doi.org/10.1152/ajpcell.00030.2004.
Texto completo da fonteResumo:
Recent results showing that large-conductance, calcium-activated K+ (BKCa) channels undergo direct tyrosine phosphorylation in the presence of c-Src tyrosine kinase have suggested the involvement of these channels in Src-mediated signaling pathways. Given the important role for c-Src in integrin-mediated signal transduction, we have examined the potential regulation of BKCa channels by proline-rich tyrosine kinase 2 (Pyk2), a calcium-sensitive tyrosine kinase activated upon integrin stimulation. Transient coexpression of murine BKCa channels with either wild-type Pyk2 or hematopoietic cell kinase (Hck), a Src-family kinase, led to an enhancement of BKCa channel activity over the range of 1–10 μM free calcium, whereas coexpression with catalytically inactive forms of either kinase did not significantly alter BKCa gating compared with channels expressed alone. In the presence of either wild-type Pyk2 or Hck, BKCa α-subunits were found to undergo tyrosine phosphorylation, as determined by immunoprecipitation and Western blotting strategies. However, tyrosine phosphorylation of the BKCa α-subunit was not detected for channels expressed alone or together with inactive forms of either Pyk2 or Hck. Interestingly, wild-type, but not inactive, Pyk2 was also present in BKCa channel immunoprecipitates, suggesting that Pyk2 may coassociate with the BKCa channel complex after phosphorylation. Collectively, the observed modulation and phosphorylation of BKCa channels by Pyk2 and a Src-family kinase may reflect a general cellular mechanism by which G protein-coupled receptor and/or integrin activation leads to the regulation of membrane ion channels.
5
Kim, Eun Young, Jae Mi Suh, Yu-Hsin Chiu e Stuart E. Dryer. "Regulation of podocyte BKCa channels by synaptopodin, Rho, and actin microfilaments". American Journal of Physiology-Renal Physiology 299, n.º 3 (setembro de 2010): F594—F604. http://dx.doi.org/10.1152/ajprenal.00206.2010.
Texto completo da fonteResumo:
Mechanosensitive large-conductance Ca2+-activated K+ channels encoded by the Slo1 gene (BKCa channels) are expressed in podocytes. Here we show that BKCa channels reciprocally coimmunoprecipitate with synaptopodin (Synpo) in mouse glomeruli, in mouse podocytes, and in a heterologous expression system (HEK293T cells) in which these proteins are transiently expressed. Synpo and Slo1 colocalize along the surface of the glomerular basement membrane in mouse glomeruli. Synpo interacts with BKCa channels at COOH-terminal domains that overlap with an actin-binding domain on the channel molecule that is necessary for trafficking of BKCa channels to the cell surface. Moreover, addition of exogenous β-actin to mouse podocyte lysates reduces BKCa-Synpo interactions. Coexpression of Synpo increases steady-state surface expression of BKCa channels in HEK293T cells. However, Synpo does not affect the stability of cell surface BKCa channels, suggesting a primary effect on the rate of forward trafficking, and Synpo coexpression does not affect BKCa gating. Conversely, stable knockdown of Synpo expression in mouse podocyte cell lines reduces steady-state surface expression of BKCa channels but does not affect total expression of BKCa channels or their gating. The effects of Synpo on surface expression of BKCa are blocked by inhibition of Rho signaling in HEK293T cells and in podocytes. Functional cell surface BKCa channels in podocytes are also reduced by sustained (2 h) but not acute (15 min) depolymerization of actin with cytochalasin D. Synpo may regulate BKCa channels through its effects on actin dynamics and by modulating interactions between BKCa channels and regulatory proteins of the podocyte slit diaphragm.
6
Werner, Matthias E., Andrea L. Meredith, Richard W. Aldrich e Mark T. Nelson. "Hypercontractility and impaired sildenafil relaxations in the BKCa channel deletion model of erectile dysfunction". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 295, n.º 1 (julho de 2008): R181—R188. http://dx.doi.org/10.1152/ajpregu.00173.2008.
Texto completo da fonteResumo:
Erectile dysfunction (ED) can be elicited by a variety of pathogenic factors, particularly impaired formation of and responsiveness to nitric oxide (NO) and the downstream effectors soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase I (PKGI). One important target of PKGI in smooth muscle is the large-conductance, Ca2+-activated potassium (BKCa) channel. In our previous report ( 42 ), we demonstrated that deletion of the BKCa channel in mice induced force oscillations and led to reduced nerve-evoked relaxations and ED. In the current study, we used this ED model to explore the role of the BKCa channel in the NO/sGC/PKGI pathway. Electrical field stimulation (EFS)-induced contractions of corpus cavernosum smooth muscle strips were significantly enhanced in the absence of BKCa channel function. In strips precontracted with phenylephrine, EFS-induced relaxations were converted to contractions by inhibition of sGC, and this was further enhanced by loss of BK channel function. Sildenafil-induced relaxations were decreased to a similar extent by inhibition of sGC or BKCa channels. At concentrations >1 μM, sildenafil caused relaxations independent of inhibition of sGC or BKCa channels. Sildenafil did not affect the enhanced force oscillations that were induced by the loss of BKCa channel function. Yet, these oscillations could be completely eliminated by blocking L-type voltage-dependent Ca2+ channels (VDCCs). These results suggest that therapeutically relevant concentrations of sildenafil act through cGMP and BKCa channels, and loss of BKCa channel function leads to hypercontractility, which depends on VDCCs and cannot be modified by the cGMP pathway.
7
Choi, Chang-Rok, Eun-Jin Kim, Tae Hyun Choi, Jaehee Han e Dawon Kang. "Enhancing Human Cutaneous Wound Healing through Targeted Suppression of Large Conductance Ca2+-Activated K+ Channels". International Journal of Molecular Sciences 25, n.º 2 (9 de janeiro de 2024): 803. http://dx.doi.org/10.3390/ijms25020803.
Texto completo da fonteResumo:
The modulation of K+ channels plays a crucial role in cell migration and proliferation, but the effect of K+ channels on human cutaneous wound healing (CWH) remains underexplored. This study aimed to determine the necessity of modulating K+ channel activity and expression for human CWH. The use of 25 mM KCl as a K+ channel blocker markedly improved wound healing in vitro (in keratinocytes and fibroblasts) and in vivo (in rat and porcine models). K+ channel blockers, such as quinine and tetraethylammonium, aided in vitro wound healing, while Ba2+ was the exception and did not show similar effects. Single-channel recordings revealed that the Ba2+-insensitive large conductance Ca2+-activated K+ (BKCa) channel was predominantly present in human keratinocytes. NS1619, an opener of the BKCa channel, hindered wound healing processes like proliferation, migration, and filopodia formation. Conversely, charybdotoxin and iberiotoxin, which are BKCa channel blockers, dramatically enhanced these processes. The downregulation of BKCa also improved CWH, whereas its overexpression impeded these healing processes. These findings underscore the facilitative effect of BKCa channel suppression on CWH, proposing BKCa channels as potential molecular targets for enhancing human cutaneous wound healing.
8
Barman, Scott A., Shu Zhu e Richard E. White. "Protein kinase C inhibits BKCa channel activity in pulmonary arterial smooth muscle". American Journal of Physiology-Lung Cellular and Molecular Physiology 286, n.º 1 (janeiro de 2004): L149—L155. http://dx.doi.org/10.1152/ajplung.00207.2003.
Texto completo da fonteResumo:
Signaling mechanisms that elevate cyclic AMP (cAMP) activate large-conductance, calcium- and voltage-activated potassium (BKCa) channels in pulmonary vascular smooth muscle and cause pulmonary vasodilatation. BKCa channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (closing) of the BKCa channel has been implicated in the development of pulmonary vasoconstriction. Protein kinase C (PKC) causes pulmonary vasoconstriction, but little is known about the effect of PKC on BKCa channel activity. Accordingly, studies were done to determine the effect of PKC activation on cAMP-induced BKCa channel activity using patch-clamp studies in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), a recognized animal model of pulmonary hypertension. Forskolin (10 μM), a stimulator of adenylate cyclase and an activator of cAMP, opened BKCa channels in single FHR PASMC, which were blocked by the PKC activators phorbol 12-myristate 13-acetate (100 nM) and thymeleatoxin (100 nM). The inhibitory response by thymeleatoxin on forskolin-induced BKCa channel activity was blocked by Gö-6983, which selectively blocks the α, β, δ, γ, and ζ PKC isozymes, and Gö-6976, which selectively inhibits PKC-α, PKC-β, and PKC-μ, but not by rottlerin, which selectively inhibits PKC-δ. Collectively, these results indicate that activation of specific PKC isozymes inhibits cAMP-induced activation of the BKCa channel in pulmonary arterial smooth muscle, which suggests a unique signaling pathway to modulate BKCa channels and subsequently cAMP-induced pulmonary vasodilatation.
9
Khan, Raheela N., Stephen K. Smith, J. J. Morrison e Michael L. J. Ashford. "Ca2+ dependence and pharmacology of large-conductance K+ channels in nonlabor and labor human uterine myocytes". American Journal of Physiology-Cell Physiology 273, n.º 5 (1 de novembro de 1997): C1721—C1731. http://dx.doi.org/10.1152/ajpcell.1997.273.5.c1721.
Texto completo da fonteResumo:
Two populations, Ca2+-dependent (BKCa) and Ca2+-independent K+ (BK) channels of large conductance were identified in inside-out patches of nonlabor and labor freshly dispersed human pregnant myometrial cells, respectively. Cell-attached recordings from nonlabor myometrial cells frequently displayed BKCa channel openings characterized by a relatively low open-state probability, whereas similar recordings from labor tissue displayed either no channel openings or consistently high levels of channel activity that often exhibited clear, oscillatory activity. In inside-out patch recordings, Ba2+ (2–10 mM), 4-aminopyridine (0.1–1 mM), and Shaker B inactivating peptide (“ball peptide”) blocked the BKCa channel but were much less effective on BK channels. Application of tetraethylammonium to inside-out membrane patches reduced unitary current amplitude of BKCa and BK channels, with dissociation constants of 46 mM and 53 μM, respectively. Tetraethylammonium applied to outside-out patches decreased the unitary conductance of BKCa and BK channels, with dissociation constants of 423 and 395 μM, respectively. These results demonstrate that the properties of human myometrial large-conductance K+channels in myocytes isolated from laboring patients are significantly different from those isolated from nonlaboring patients.
10
Hou, Shangwei, Stefan H. Heinemann e Toshinori Hoshi. "Modulation of BKCa Channel Gating by Endogenous Signaling Molecules". Physiology 24, n.º 1 (fevereiro de 2009): 26–35. http://dx.doi.org/10.1152/physiol.00032.2008.
Texto completo da fonteResumo:
Large-conductance Ca2+- and voltage-activated K+ (BKCa, MaxiK, or Slo1) channels are expressed in almost every tissue in our body and participate in many critical functions such as neuronal excitability, vascular tone regulation, and neurotransmitter release. The functional versatility of BKCa channels owes in part to the availability of a spectacularly wide array of biological modulators of the channel function. In this review, we focus on modulation of BKCa channels by small endogenous molecules, emphasizing their molecular mechanisms. The mechanistic information available from studies on the small naturally occurring modulators is expected to contribute to our understanding of the physiological and pathophysiological roles of BKCa channels.
Teses / dissertações sobre o assunto "BKCa channels"
1
McCartney, Claire Elizabeth. "Effect of hypoxia on neuronal large conductance calcium-activated potassium (BKca) channels". Thesis, University of Strathclyde, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410156.
Texto completo da fonte
2
Ferraguto, Celeste. "BKCa channels as therapeutic targets in neurodevelopmental disorders : focus on acoustic dysfunction". Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0134.
Texto completo da fonteResumo:
Les troubles du neurodéveloppement (TNDs) se caractérisent par un vaste éventail de phénotypes pathologiques qui englobent diverses anomalies aussi bien physiques, cérébrales que comportementales. Parmi celles-ci, les altérations de la perception auditive sont fréquemment observées dans plusieurs TNDs. L’existence de cette symptomatologie commune suggère que des mécanismes sous-jacents comparables seraient à l’origine des TNDs, et donc que des stratégies thérapeutiques similaires pourraient permettre de palier les déficits observés. Malgré des efforts considérables, des composés pharmacologiques efficaces pour le traitement de la plupart des TNDs font toujours défaut, rendant plus que jamais nécessaire le développement de nouveaux médicaments ou l’identification de nouvelles indications thérapeutiques pour des médicaments existants (repositionnement). Le dysfonctionnement des canaux potassiques de grande conductance activés par le calcium (canaux BKCa) a émergé comme un mécanisme pathologique clé potentiellement impliqué dans plusieurs TNDs. Ces canaux ubiquitaires modulent l'activité des cellules excitables, incluant les neurones, les cellules musculaires lisses et cardiaques, ainsi que les cellules ciliées de la cochlée, leur conférant un rôle prépondérant dans les fonctions synaptiques, cardiovasculaires et auditives. Une réduction de l’expression et de la fonctionnalité des canaux BKCa est notamment observée chez les patients atteints de deux TNDs majeurs, à savoir les syndromes de l'X fragile (SXF) et de Williams-Beuren (SWB), suggérant que des composés activant ces canaux pourraient constituer des traitements prometteurs pour ces deux syndromes d’origine génétique. Dans ce contexte, ce travail de thèse a consisté à caractériser, à l’échelle préclinique, le potentiel thérapeutique du Chlorzoxazone, un activateur des canaux BKCa, pour traiter les phénotypes pathologiques associés aux SXF et SWB. Pour ce faire, nous avons utilisé les lignées de souris mutantes Fmr1-KO et CD qui reproduisent la plupart des symptômes observés chez les patients respectivement SXF et SWB, y compris les altérations des canaux BKCa. Dans la première partie de la thèse, nous avons combiné des paradigmes comportementaux, notamment des tests moteurs, émotionnels et sociaux, avec l'analyse de marqueurs de plasticité neuronale, tels que l’analyse des dendrites, les niveaux de neurotrophines et l'expression du facteur de transciption c-fos dans des régions cérébrales spécifiques. Chez les souris CD, nous avons également caractérisé les phénotypes cardiovasculaires typiques du SWB, à savoir l'hypertrophie cardiaque et la sténose aortique. Nos résultats montrent que le Chlorzoxazone, administré de manière aiguë ou chronique, permet de traiter efficacement les divers phénotypes pathologiques présents chez les mutants Fmr1-KO et CD. Dans la deuxième partie, nous nous sommes concentrés sur les altérations auditives observées chez les deux modèles de souris et nous avons révélé l'efficacité globale du Chlorzoxazone à rétablir ces anomalies aux niveaux électrophysiologique (émissions otoacoustiques), structurel (intégrité des cellules ciliées de la cochlée et des synapses à ruban) et comportemental (réflexe du sursaut acoustique). Dans l'ensemble, nos résultats identifient les canaux BKCa comme une cible thérapeutique prometteuse pour le traitement du SXF et du SWB, ainsi que des dysfonctionnements auditifs associés. De plus, ils plaident en faveur du repositionnement du Chlorzoxazone, un médicament déjà sur le marché pour le traitement des pathologies musculaires, à des fins cliniques dans le contexte des TNDs. En conclusion, cette thèse constitue une base préclinique solide pour de futurs essais cliniques chez les patients atteints du SXF et du SWB et démontre l’intérêt de conduire davantage de recherches précliniques sur le rôle des canaux BKCa dans les dysfonctionnements auditifs et comportementauxNeurodevelopmental disorders (NDDs) are typically characterized by a range of pathological phenotypes, encompassing a variety of physical, brain, and behavioral abnormalities. Among these, impaired auditory perception and hearing alterations are commonly observed across multiple NDDs. Given the presence of shared symptomatology, increasing interest is devoted to the identification of potential common underlying mechanisms and, therefore, shared therapeutic strategies. Despite extensive efforts, effective pharmacological interventions for most NDDs are still lacking, prompting research on novel drugs, as well as on repurposed treatments. Dysfunction in big conductance calcium-activated potassium (BKCa) ion channels has emerged as a potential key pathological mechanism involved in multiple NDDs: these ubiquitous channels play a pivotal role in modulating the activity of excitable cells, including neurons, vascular smooth muscle, and cardiac cells, as well as cochlear hair cells, thus being strongly implicated in synaptic, cardio-vascular and auditory functions. Notably, reduced expression and functionality of BKCa channels have been documented in patients with two major NDDs, i.e., fragile X and Williams-Beuren syndromes (FXS and WBS), suggesting that compounds activating these channels could offer promising treatments for these two genetic syndromes. This thesis aimed to provide preclinical evidence supporting the therapeutic potential of Chlorzoxazone, an FDA-approved BKCa channel opener, for treating the pathological phenotypes of FXS and WBS. To this end, we employed the Fmr1-KO and the CD mouse lines, representing the main preclinical models of FXS and WBS, respectively, which recapitulate most symptoms displayed by patients, including BKCa channel expression and functional deficits. In the first part of the thesis, we demonstrated that Chlorzoxazone, administered either acutely or chronically, effectively treated various behavioral, brain, and physical phenotypes exhibited by Fmr1-KO and CD mutants. To this aim, we combined behavioral assessments of both mutant mouse lines, encompassing motor, emotional, and social tests, with the analysis of markers of neuronal plasticity and functionality, e.g., dendritic abnormalities, neurotrophin levels, and fos expression in specific brain regions. Additionally, in the CD mouse model, we characterized cardiovascular phenotypes typical of WBS, i.e., cardiac hypertrophy and aortic stenosis. In the second part, we focused on the auditory alterations displayed by the two mouse models and we showed the overall efficacy of Chlorzoxazone in rescuing these abnormalities at electrophysiological, structural, and behavioral levels. This involved assessing auditory brainstem responses and distortion product otoacoustic emissions, alongside the immuno-histochemical evaluation of cochlear hair cells and ribbon synapses, and behavioral analysis of the acoustic startle response. Overall, our findings support BKCa channels as promising therapeutic targets for FXS and WBS, as well as for associated auditory dysfunctions. Furthermore, they advocate for repurposing Chlorzoxazone, already on the market for muscular pathologies, for clinical use in the context of NDDs. In conclusion, this thesis provides a preclinical foundation for future clinical trials in FXS and WBS and encourages further preclinical research into the role of BKCa channels in auditory and behavioral dysfunction
3
Krishnamoorthy, Gayathri. "MECHANISM OF CALCIUM DEPENDENT GATING OF BKCa CHANNELS: RELATING PROTEIN STRUCTURE TO FUNCTION". online version, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1144444855.
Texto completo da fonte
4
Sane, Mukta. "Role of Large Conductance, Calcium-Activated Potassium Channels (BKCa) in Vasorelaxation of Nitrate Tolerant Mesenteric Arteries". Diss., North Dakota State University, 2016. http://hdl.handle.net/10365/25665.
Texto completo da fonte
5
Ayad, Oualid. "Caractérisation fonctionnelle des cellules souches cardiaques humaines dans un but thérapeutique". Thesis, Poitiers, 2017. http://www.theses.fr/2017POIT2303/document.
Texto completo da fonteResumo:
L'objectif de cette thèse était de développer et de caractériser un modèle de cellules souches cardiaques humaines dans un contexte de thérapie cellulaire. Après avoir sélectionné et caractérisé une population de cellules souches d'origine mésenchymateuse, isolée à partir d'auricules humaines, exprimant le marqueur W8B2 (CSCs W8B2+), nous nous sommes focalisés (par les techniques de RT-qPCR à haut rendement, d'immuno-marquage, de western-blot et de fluorescence calcique) sur ; 1. la caractérisation génique des canaux ioniques et des acteurs de la signalisation calcique et 2. l'étude de leur différenciation in vitro en parallèle à l'activité calcique intracellulaire. Les résultats montrent que CSCs W8B2+ tendent à se différencier en cellules pacemaker. Certains gènes spécifiques nodaux, comme Tbx3, HCN, ICaT,L, Kv, NCX, s'expriment durant la différenciation. L'enregistrement de l'activité calcique (via une sonde optogénétique) montre la présence d'oscillations calciques qui évoluent en fréquence et en intensité pendant la différenciation. Les stocks-IP3 sensibles et l'échangeur NCX joueraient un rôle fondamental.Nous avons ensuite étudié l'importance du canal BKCa et des récepteurs sphingosine 1-phosphate (S1P) dans la régulation des propriétés fondamentales des CSCs W8B2+. L'inhibition du BKCa diminue la prolifération cellulaire en accumulant les cellules à la phase G0/G1, réprime l'auto-renouvellement mais n'affecte pas la migration. Quant à la S1P elle freine la prolifération et l'auto-renouvellement via une voie différente de celles des récepteurs S1P1,2,3.Ce travail fait ressortir des cibles moléculaires fondamentales dans un contexte de thérapie cellulaire cardiaqueThe aim of this thesis was to develop and characterize a model of human heart stem cells in a context of cell therapy.A population of mesenchymal stem cells, expressing the W8B2 marker (CSCs W8B2+), was first isolated from human auricles and characterized using high-throughput RT-qPCR techniques, immuno-labeling, western-blot and calcium fluorescence imaging. These experiments were focused on 1. the gene expression of ion channels and calcium signaling proteins; and 2. the study of CSCs W8B2+ in vitro differentiation and associated intracellular calcium activity changes.The results show that CSCs W8B2+ tend to differentiate into pacemaker cells. Some nodal specific genes such as Tbx3, HCN, ICaT, L, Kv, NCX, are expressed during differentiation. The recording of calcium activity (via an optogenetic probe) shows the presence of calcium oscillations that change in frequency and intensity during differentiation. IP3 sensitive calcium stocks and the NCX exchanger would play a fundamental role in these variations.Then we studied the importance of the BKCa channel and the sphingosine 1-phosphate (S1P) receptors in the regulation of the fundamental properties of the W8B2+ CSCs. Inhibition of BKCa reduces cell proliferation by accumulating cells in the G0 / G1 phase, suppresses cell self-renewal but does not affect migration properties. Concerning S1P, it decreases proliferation and self-renewal without stimulate S1P1,2,3 receptors.This work highlights fundamental potential molecular targets in a context of cardiac cell therapy
6
Gambade, Audrey. "Rôle du peptide LL-37 dans le cancer du sein : son interaction avec la membrane plasmique stimule l'entrée de calcium et la migration cellulaire par l'activation des canaux ioniques TRPV2 et BKCa". Thesis, Tours, 2015. http://www.theses.fr/2015TOUR3312/document.
Texto completo da fonteResumo:
Le peptide antimicrobien LL-37 a été retrouvé surexprimé dans différents types de cancer et plus particulièrement dans le cancer du sein dans lequel il est associé au développement des métastases. Nous avons observé, in vitro, que la migration de trois lignées cancéreuses mammaires est augmentée par le peptide LL-37 et son énantiomère (D)-LL-37, excluant la fixation du peptide à un récepteur protéique. Sur les cellules cancéreuses mammaires MDA-MB-435s, le peptide se fixe à la membrane plasmique et diminue sa fluidité. La microscopie électronique localise LL-37 dans les cavéoles et à la surface de structures impliquées dans la migration cellulaire, les pseudopodes. LL-37 induit une entrée de calcium via le canal TRPV2 dont l’activité est augmentée par son recrutement dans les pseudopodes. Ce recrutement est dépendant de l’activation de la voie de signalisation PI3K/AKT induite par LL-37. L’entrée de calcium via TRPV2 est potentialisée par l’activation du canal potassique BKCa, localisé aussi dans les pseudopodes. Des ARN interférents contre TRPV2 inhibent à 70% la migration induite par LL-37, donnant un rôle prépondérant à ce canal dans les effets pro-migratoire du peptide. La fixation du peptide LL-37 aux membranes des cellules cancéreuses et l’activation de canaux ioniques constituent un nouvel axe de recherche pour comprendre le rôle du peptide dans la progression tumoraleThe antimicrobial peptide LL-37 is overexpressed in several types of cancer, among which breast cancer were it is associated with metastasis development. Our experiments on three mammary cancer cell lines have shown that LL-37 increases cell migration. Both its natural (L)-form and its (D)-enantiomer are equally active, excluding a specific binding to a protein receptor. On the MDA-MB-435s cell line, LL-37 attaches to plasma membrane and reduces its fluidity. Electron microscopy localized LL-37 on the surface of pseudopodia, structures implicated in cell migration, and in caveolae. LL-37 induces calcium entry via the TRPV2 channel, which is recruited to pseudopodia. Recruitment depends on activation of PI3K/AKT signaling induced by LL-37. Calcium entry via TRPV2 is potentiated by activation of the BKCa potassium channel also located in pseudopodia. TRPV2 suppression by RNA interference results in 70% reduction of cell migration induced by LL-37, attributing a crucial role of this channel to the promigratory effects of the peptide. Binding of LL-37 to cancer cell membranes and in consequence the activation of ion channels constitutes a novel research field to understand its role in tumor progression
7
Hdud, Ismail Masaud M. "Expression of TRPV channel isoforms and BKCa channel subunits in equine articular chondrocytes and their potential role in cartilage biology and cellular pathology". Thesis, University of Nottingham, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662204.
Texto completo da fonteResumo:
Mechanical injuries play an important role in the pathogenesis of osteoarthritis, especially in horses. Chondrocytes are highly mechanosensitive cells responsible for the production and maintenance of the extracellular matrix (ECM) of articular cartilage. ECM turnover is influenced by mechanical and osmotic factors, and Ca 2+ signalling is a key component of mechanical responsiveness in these cells. Hence, for this thesis, freshly isolated equine articular chondrocytes was used to investigate the influence of mechanical and/or osmotic loading. Immunohistochemistry revealed superficial localisation of the TRPV (Transient Receptor Potential Vanilloid) channel members 4, 5 and 6 in equine articular cartilage suggesting a possible mechanotransduction and chemotransduction role for these channels in articular chondrocytes. Furthermore, in serial passages, the expression of TRPV4 and BKca channels were stable whereas expression of the TRPVS and 6 channels increased with time and the number of passages, which correlated with de-differentiation of chondrocytes.
8
Azhikkattuparambil, Bhaskaran Arjun. "Cellular and circuit mechanisms of neocortical dysfunction in Fragile X Syndrome". Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0244/document.
Texto completo da fonteResumo:
Cette étude explore les réponses évoquées, l'activité intrinsèque et spontanée de deux populations neuronales différentes dans la région du cerveau correspondant à la patte arrière des souris. Dans cet article, nous nous sommes concentrés sur un modèle murin du syndrome de l'X fragile (SXF), qui est la forme la plus commune de syndrome de retard mental héréditaire et une cause fréquente de troubles du spectre autistique (TSA). SXF est un trouble à gène unique (Fmr1), qui peut être modélisé de manière fiable par un modèle murin transgénique : la souris Fmr1-/y déficiente pour le gène codant Fmr1. L'hyperexcitabilité des réseaux néocorticaux et l'hypersensibilité aux stimuli sensoriels sont des caractéristiques importantes du SXF et des TSA.Ceci est directement lié à un changement du nombre de synapses locales, de canaux ioniques, de l'excitabilité membranaire et de la connectivité des circuits de cellules individuelles. Précédemment, nous avons identifié un défaut dans les canaux ioniques, comme pouvant contribuer à ces phénotypes. Nous avons testé cette hypothèse comme un mécanisme contribuant aux défauts de traitement sensoriel chez les souris Fmr1-/y. Le cortex somatosensoriel primaire de la souris (S1) traite différentes informations sensorielles et constitue la plus grande zone du néocortex, soulignant l'importance de la modalité sensorielle pour le comportement des rongeurs. Nos connaissances concernant le traitement de l'information dans S1 proviennent d'études du cortex en tonneaux lié aux moustaches, mais le traitement des entrées sensorielles des pattes postérieures est mal compris. Par l’utilisation de la technique d’enregistrement de cellule entière par patch clamp in vivo, nous avons classes les cellules en répondeurs supraliminaires (cellules qui répondaient aux stimulations de la patte arrière avec un potentiel d'action), les répondeurs subliminaires (les cellules qui répondaient sans déclencher un potentiel d'action) et les cellules non répondeuses qui ne présentaient aucune réponse. Puis, nous avons comparé les réponses évoquées sub et supraliminaires, les propriétés intrinsèques et l’activité spontanée des neurones pyramidaux de la couche 2/3 (L2/3) de la region S1 de la patte arrière (S1-HP) d’animaux anesthésiés sauvage (WT) et Fmr1-/y. Nous avons identifié des altérations de réponse spontanée, intrinsèque et évoquée chez les souris Fmr1-/y. L’application d’un ouvreur de canaux ioniques BKCa a restauré certaines de ces propriétés altérées chez les souris Fmr1-/yThis study explores the evoked responses, intrinsic and spontaneous activity of two different neuronal populations in the hind paw region of the primary somatosensory cortex (S1) of mice. Initially, we explored information processing in these neurons under normal physiological conditions, and subsequently in a mouse model of Fragile X Syndrome (FXS). FXS is the most common form of inherited mental retardation syndrome and a frequent cause of autism spectrum disorders (ASD). FXS is a single gene (Fmr1) disorder, which can be reliably modeled by a mutant mouse model, the Fmr1 knockout (Fmr1-/y) mouse. Hyperexcitability of neocortical networks and hypersensibility to sensory stimuli are prominent features of FXS and ASD. We previously established a strong causal link between a channelopathy, hyperexcitability of neurons in the primary sensory region of the neocortex and sensory hypersensitivity in this mouse model. In the current study, we extended these findings, by conducting a detailed exploration of the processing of tactile sensory information (evoked by hind paw stimulation) in the neocortex of these mice.Most of our knowledge regarding information processing in S1 comes from studies of the whisker-related barrel cortex (which processes tactile-related sensory information derived from the whiskers), yet the processing of sensory inputs from the hind-paws is poorly understood. Using in vivo whole-cell patch-clamp recordings, we classified the cells into suprathreshold responders (the cells which responded to the hind-paw stimulations with an action potential), subthreshold responders (the cells responded without eliciting an action potential) and non-responder cells (neurons which did not show any response). We then compared the evoked sub- and supra-threshold responses, intrinsic properties, and spontaneous activity of layer (L) 2/3 pyramidal neurons of the S1 hind-paw (S1-HP) region of anaesthetized wild type (WT) and Fmr1-/y mice. We identified spontaneous, intrinsic and evoked response alterations in Fmr1-/y mice. We probed possible mechanisms contributing to this sensory impairment in Fmr1-/y mice. Finally, we tested the possibility of correcting pathophysiological alterations in these neurons using specific pharmacological agents targeting the ion channel defects described previously by our team
9
"TRPV4-TRPC1- BKca tri-complex mediates epoxyeicosatrienoic acid-induced membrane hyperpolarization". Thesis, 2011. http://library.cuhk.edu.hk/record=b6075501.
Texto completo da fonteResumo:
Ma, Yan."Ca" in the title is subscript.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 143-166).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
10
Chien-Fu, Chen. "Eugenosedin-A activates BKCa channels in rat basilar artery myocytes". 2005. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0011-2903200614032202.
Texto completo da fonteCapítulos de livros sobre o assunto "BKCa channels"
1
Telezhkin, V., S. P. Brazier, S. Cayzac, C. T. Müller, D. Riccardi e P. J. Kemp. "Hydrogen Sulfide Inhibits Human BKCa Channels". In Advances in Experimental Medicine and Biology, 65–72. Dordrecht: Springer Netherlands, 2009. http://dx.doi.org/10.1007/978-90-481-2259-2_7.
Texto completo da fonte
2
Vaithianathan, Thirumalini, Elizabeth H. Schneider, Anna N. Bukiya e Alex M. Dopico. "Cholesterol and PIP2 Modulation of BKCa Channels". In Advances in Experimental Medicine and Biology, 217–43. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-21547-6_8.
Texto completo da fonte
3
de Wet, Heidi, Jonathan D. Lippiat e Marcus Allen. "Analysing Steroid Modulation of BKCa Channels Reconstituted into Planar Lipid Bilayers". In Methods in Molecular Biology, 177–86. Totowa, NJ: Humana Press, 2008. http://dx.doi.org/10.1007/978-1-59745-526-8_14.
Texto completo da fonte
4
Neira, Fernanda, Nataly Neira, Javier Torres e Marcelo González-Ortiz. "Physiological and Pathophysiological Role of Large-Conductance Calcium-Activated Potassium Channels (BKCa) in HUVECs and Placenta". In Advances in Maternal-Fetal Biomedicine, 71–82. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-32554-0_3.
Texto completo da fonte
5
Kolář, František. "Mitochondrial BKCa Channel as a Target for Cardioprotection". In NATO Science for Peace and Security Series A: Chemistry and Biology, 163–75. Dordrecht: Springer Netherlands, 2013. http://dx.doi.org/10.1007/978-94-007-6513-9_13.
Texto completo da fonte
6
Jia, Xiaoling, Jingyun Yang, Liu Yang, Ping Li, Wei Song e Yubo Fan. "Irrelevance of BKCa Channel Expression to VSMCs Phenotype under Shear Stress". In IFMBE Proceedings, 206–9. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-29305-4_56.
Texto completo da fonte
7
Edwards, Gillian, e Arthur H. Weston. "The Pharmacology of Potassium Channel Superfamilies: Modulation of KATP and BKCa". In Molecular and Cellular Mechanisms of Cardiovascular Regulation, 93–109. Tokyo: Springer Japan, 1996. http://dx.doi.org/10.1007/978-4-431-65952-5_9.
Texto completo da fonte
8
Brazier, S. P., V. Telezhkin, R. Mears, C. T. Müller, D. Riccardi e P. J. Kemp. "Cysteine Residues in the C-terminal Tail of the Human BKCaα Subunit Are Important for Channel Sensitivity to Carbon Monoxide". In Advances in Experimental Medicine and Biology, 49–56. Dordrecht: Springer Netherlands, 2009. http://dx.doi.org/10.1007/978-90-481-2259-2_5.
Texto completo da fonte
9
Santiago, Jorge, Cristhian Romero, Santiago Guerrero, Francisco Trejo e Daniel Robles. "Bio-Informatic Model of Tyrosine Kinases Inhibitors in Trabecular Meshwork Cells". In Frontiers in Artificial Intelligence and Applications. IOS Press, 2021. http://dx.doi.org/10.3233/faia210034.
Texto completo da fonteResumo:
The behavior of potassium ion (K+) establishes the repolarization and hyperpolarization states in the cell membrane of trabecular meshwork cells. One of the main proteins that controls this ion is calcium-dependent potassium maxi-channels BKca, their malfunction evoked by tyrosine kinases, destabilize the control of aqueous humor flow and the increase of intraocular pressure, responsible of glaucoma. In the present work, the ionic behavior of ion K+ of trabecular cells is detailed, when genistein and tyrphostin-51 are applied in culture cells. The flow behavior is described by means of mathematical expressions based on exponential functions and equations of line. Genistein and tyrphostin-51 drugs are compared in their efficiency of inhibiting tyrosine kinases from the mathematical functions provided by the proposed method. The present study describes the ion behavior regarding K+ potassium which is controlled by maxi-channels BKca that come from trabecular meshwork when genistein and tyrphostin-51 are applied in culture cells. The behavior of this flow is described by mathematical expressions. Thus, inhibitor drugs effect and characteristic time behavior are compared using their mathematical function.
10
Fajmut, Aleš. "Molecular Mechanisms and Targets of Cyclic Guanosine Monophosphate (cGMP) in Vascular Smooth Muscles". In Muscle Cell and Tissue - Novel Molecular Targets and Current Advances [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.97708.
Texto completo da fonteResumo:
Molecular mechanisms and targets of cyclic guanosine monophosphate (cGMP) accounting for vascular smooth muscles (VSM) contractility are reviewed. Mathematical models of five published mechanisms are presented, and four novel mechanisms are proposed. cGMP, which is primarily produced by the nitric oxide (NO) dependent soluble guanylate cyclase (sGC), activates cGMP-dependent protein kinase (PKG). The NO/cGMP/PKG signaling pathway targets are the mechanisms that regulate cytosolic calcium ([Ca2+]i) signaling and those implicated in the Ca2+-desensitization of the contractile apparatus. In addition to previous mathematical models of cGMP-mediated molecular mechanisms targeting [Ca2+]i regulation, such as large-conductance Ca2+-activated K+ channels (BKCa), Ca2+-dependent Cl− channels (ClCa), Na+/Ca2+ exchanger (NCX), Na+/K+/Cl− cotransport (NKCC), and Na+/K+-ATPase (NKA), other four novel mechanisms are proposed here based on the existing but perhaps overlooked experimental results. These are the effects of cGMP on the sarco−/endo- plasmic reticulum Ca2+-ATPase (SERCA), the plasma membrane Ca2+-ATPase (PMCA), the inositol 1,4,5-trisphosphate (IP3) receptor channels type 1 (IP3R1), and on the myosin light chain phosphatase (MLCP), which is implicated in the Ca2+-desensitization. Different modeling approaches are presented and discussed, and novel model descriptions are proposed.
Trabalhos de conferências sobre o assunto "BKCa channels"
1
Guntur, D., D. Jeremic, V. Foris, H. Olschewski, A. Olschewski e C. Nagaraj. "Relevance of BKCa Channels in Pulmonary Endothelial Dysfunction". In American Thoracic Society 2024 International Conference, May 17-22, 2024 - San Diego, CA. American Thoracic Society, 2024. http://dx.doi.org/10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4042.
Texto completo da fonte
2
Zhu, Shu, Richard E. White, Mary L. Meadows e Scott A. Barman. "Expression Of BKCa Channels In Pulmonary Arterial Smooth Muscle And The Effect Of Protein Kinase C Phosphorylation Site S1076 On The Response To PKCµ On BKCa Channel Activity". In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a6449.
Texto completo da fonte