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1

Art, J. J., Y. C. Wu, and R. Fettiplace. "The calcium-activated potassium channels of turtle hair cells." Journal of General Physiology 105, no. 1 (1995): 49–72. http://dx.doi.org/10.1085/jgp.105.1.49.

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A major factor determining the electrical resonant frequency of turtle cochlear hair cells is the time course of the Ca-activated K current (Art, J. J., and R. Fettiplace. 1987. Journal of Physiology. 385:207-242). We have examined the notion that this time course is dictated by the K channel kinetics by recording single Ca-activated K channels in inside-out patches from isolated cells. A hair cell's resonant frequency was estimated from its known correlation with the dimensions of the hair bundle. All cells possess BK channels with a similar unit conductance of approximately 320 pS but with d
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2

Zang, Kai, Yuwen Zhang, Jie Hu, and Yun Wang. "The Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) and Epilepsy." CNS & Neurological Disorders - Drug Targets 17, no. 4 (2018): 248–54. http://dx.doi.org/10.2174/1871527317666180404104055.

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Background & Objective: The large conductance, calcium- and voltage-activated potassium channels (BK) are widely distributed channel proteins which exist in virtually every cell type of mammals and function to influence membrane excitability and Ca2+ signaling. BK channels can be activated by the increase of the intracellular Ca2+ concentration, a consequence of neuronal excitation, and then terminate the action potential with the outward K+ flux. Moreover, after-hyperpolarization induced by BK channels closes Cav channels and thus precludes excessive Ca2+ influx. Considering this negative
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3

Chen, Xinzhe. "Research progress on calcium-activated potassium ion channels." Theoretical and Natural Science 62, no. 1 (2024): 160–65. http://dx.doi.org/10.54254/2753-8818/62/20241522.

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Abstract. Potassium ion channels are diverse and widely distributed, playing a key role in a variety of physiological and pathological processes. According to the size of the conductance, they can be divided into large conductive calcium activated potassium channel (BK channel), medium conductive calcium activated potassium channel (IK channel) and small conductive calcium activated potassium channel (SK channel). In recent years, remarkable progress has been made in studying these three ion channels, and a series of therapeutic drugs have emerged. According to the single channel conductance,
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4

Lara, Jesús, Juan José Acevedo, and Carlos G. Onetti. "Large-Conductance Ca2+-Activated Potassium Channels in Secretory Neurons." Journal of Neurophysiology 82, no. 3 (1999): 1317–25. http://dx.doi.org/10.1152/jn.1999.82.3.1317.

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Large-conductance Ca2+-activated K+ channels (BK) are believed to underlie interburst intervals and contribute to the control of hormone release in several secretory cells. In crustacean neurosecretory cells, Ca2+entry associated with electrical activity could act as a modulator of membrane K+ conductance. Therefore we studied the contribution of BK channels to the macroscopic outward current in the X-organ of crayfish, and their participation in electrophysiological activity, as well as their sensitivity toward intracellular Ca2+, ATP, and voltage, by using the patch-clamp technique. The BK c
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5

McKay, M. C., S. I. Dworetzky, N. A. Meanwell, et al. "Opening of large-conductance calcium-activated potassium channels by the substituted benzimidazolone NS004." Journal of Neurophysiology 71, no. 5 (1994): 1873–82. http://dx.doi.org/10.1152/jn.1994.71.5.1873.

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1. We used electrophysiological techniques to examine the effects of 5-trifluoromethyl-1-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-2H-benzimidaz ole- 2-one (NS004) on large-conductance calcium-activated potassium (BK) channels. 2. We used recordings from excised membrane patches (cell-attached and inside-out single-channel configurations) and whole-cell patch-clamp recordings to examine the effects of NS004 on single BK channels and whole-cell outward currents, respectively, in rat GH3 clonal pituitary tumor cells. We also tested NS004 on voltage-clamped BK channels isolated from rat brain plasma
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6

Pérez, Guillermo J., Mayurika Desai, Seth Anderson, and Fabiana S. Scornik. "Large-conductance calcium-activated potassium current modulates excitability in isolated canine intracardiac neurons." American Journal of Physiology-Cell Physiology 304, no. 3 (2013): C280—C286. http://dx.doi.org/10.1152/ajpcell.00148.2012.

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We studied principal neurons from canine intracardiac (IC) ganglia to determine whether large-conductance calcium-activated potassium (BK) channels play a role in their excitability. We performed whole cell recordings in voltage- and current-clamp modes to measure ion currents and changes in membrane potential from isolated canine IC neurons. Whole cell currents from these neurons showed fast- and slow-activated outward components. Both current components decreased in the absence of calcium and following 1–2 mM tetraethylammonium (TEA) or paxilline. These results suggest that BK channels under
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7

Maqoud, Fatima, Michela Cetrone, Antonietta Mele, and Domenico Tricarico. "Molecular structure and function of big calcium-activated potassium channels in skeletal muscle: pharmacological perspectives." Physiological Genomics 49, no. 6 (2017): 306–17. http://dx.doi.org/10.1152/physiolgenomics.00121.2016.

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The large-conductance Ca2+-activated K+ (BK) channel is broadly expressed in various mammalian cells and tissues such as neurons, skeletal muscles (sarco-BK), and smooth muscles. These channels are activated by changes in membrane electrical potential and by increases in the concentration of intracellular calcium ion (Ca2+). The BK channel is subjected to many mechanisms that add diversity to the BK channel α-subunit gene. These channels are indeed subject to alternative splicing, auxiliary subunits modulation, posttranslational modifications, and protein-protein interactions. BK channels can
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8

Starrett Jr., John E., Steven I. Dworetzky, and Valentin K. Gribkoff. "Modulators of Large-Conductance Calcium-Activated Potassium (BK) Channels as Potential Therapeutic Targets." Current Pharmaceutical Design 2, no. 4 (1996): 413–28. http://dx.doi.org/10.2174/1381612802666220926184514.

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BK channels are large conductance calcium-activated potassium channels that are found in many tissues, including excitable cells such as myocytes and neurons. The high conductance and dependence on calcium of BK channels suggests that modulation of these channels may have a pronounced effect on tissues in which they are expressed. Within the past four years, a variety of small molecules and natural product-derived modulators of BK channels have been described. This review will focus on compounds which are openers and blockers of BK channels and their therapeutic potential, with introductory se
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9

Feng, Xinghua, Zhuangzhuang Zhao, Qian Li, and Zhiyong Tan. "Lysosomal Potassium Channels: Potential Roles in Lysosomal Function and Neurodegenerative Diseases." CNS & Neurological Disorders - Drug Targets 17, no. 4 (2018): 261–66. http://dx.doi.org/10.2174/1871527317666180202110717.

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Background & Objective: The lysosome is a membrane-enclosed organelle widely found in every eukaryotic cell. It has been deemed as the stomach of the cells. Recent studies revealed that it also functions as an intracellular calcium store and is a platform for nutrient-dependent signal transduction. Similar with the plasma membrane, the lysosome membrane is furnished with various proteins, including pumps, ion channels and transporters. So far, two types of lysosomal potassium channels have been identified: large-conductance and Ca2+-activated potassium channel (BK) and TMEM175. TMEM175 has
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10

Hunsberger, Michael S., and Michelle Mynlieff. "BK potassium currents contribute differently to action potential waveform and firing rate as rat hippocampal neurons mature in the first postnatal week." Journal of Neurophysiology 124, no. 3 (2020): 703–14. http://dx.doi.org/10.1152/jn.00711.2019.

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This work describes the early developmental trends of large-conductance calcium-activated potassium (BK) channel activity. Early developmental trends in expression of BK channels, both total expression and relative isoform expression, have been previously reported, but little work describes the effect of these changes in expression patterns on excitability. Here, we show that early changes in BK channel expression patterns lead to changes in the role of BK channels in determining the action potential waveform and neuronal excitability.
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11

Chen, Abby L., Ting-Hsuan Wu, Lingfang Shi, William T. Clusin, and Peter N. Kao. "Calcium-Activated Big-Conductance (BK) Potassium Channels Traffic through Nuclear Envelopes into Kinocilia in Ray Electrosensory Cells." Cells 12, no. 17 (2023): 2125. http://dx.doi.org/10.3390/cells12172125.

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Electroreception through ampullae of Lorenzini in the little skate, Leucoraja erinacea, involves functional coupling between voltage-activated calcium channels (CaV1.3, cacna1d) and calcium-activated big-conductance potassium (BK) channels (BK, kcnma1). Whole-mount confocal microscopy was used to characterize the pleiotropic expression of BK and CaV1.3 in intact ampullae. BK and CaV1.3 are co-expressed in electrosensory cell plasma membranes, nuclear envelopes and kinocilia. Nuclear localization sequences (NLS) were predicted in BK and CaV1.3 by bioinformatic sequence analyses. The BK NLS is b
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12

Horrigan, Frank T. "Conformational coupling in BK potassium channels." Journal of General Physiology 140, no. 6 (2012): 625–34. http://dx.doi.org/10.1085/jgp.201210849.

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Large conductance calcium- and voltage-dependent BK potassium channels (aka BKCa, MaxiK, Slo1, KCa1.1, and KCNMA1) are expressed in a wide variety of tissues throughout the body and are activated by both intracellular Ca2+ and membrane depolarization. Owing to these properties, BK channels participate in diverse physiological processes from electrical excitability in neurons and secretory cells, and regulation of smooth muscle tone to tuning of auditory hair cells (Vergara et al., 1998; Ghatta et al., 2006). The response to voltage and Ca2+ allows BK channels to integrate electrical and calciu
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13

McCobb, D. P., N. L. Fowler, T. Featherstone, et al. "A human calcium-activated potassium channel gene expressed in vascular smooth muscle." American Journal of Physiology-Heart and Circulatory Physiology 269, no. 3 (1995): H767—H777. http://dx.doi.org/10.1152/ajpheart.1995.269.3.h767.

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Large-conductance Ca(2+)-activated K+ (BK) channels are widespread and functionally heterogeneous. In other classes of K+ channels, functional heterogeneity derives from large gene families, alternative splicing, heterologous subunit composition, and functional modulation. The molecular basis of mammalian BK channel heterogeneity is unknown, since only a single gene (mSlo) has been identified. BK channels in native vascular smooth muscle have an apparent Ca2+ sensitivity approximately 10-fold greater than native brain or skeletal muscle channels, or cloned mSlo channels. Using mSlo as a low-st
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14

Liu, Bo, Anette M. Freyer, and Ian P. Hall. "Bradykinin activates calcium-dependent potassium channels in cultured human airway smooth muscle cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 292, no. 4 (2007): L898—L907. http://dx.doi.org/10.1152/ajplung.00461.2005.

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Bradykinin (BK) is an inflammatory mediator that can cause bronchoconstriction. In this study, we investigated the membrane currents induced by BK in cultured human airway smooth muscle (ASM) cells. Depolarization of the cells induced outward currents, which were inhibited by tetraethylammonium (TEA) in a concentration-dependent manner with an IC50 of 0.33 μM. The currents were increased by elevating intracellular free Ca2+ concentration, suggesting they are calcium-activated potassium channels [ IK(Ca)]. Preexposure to inhibitor of IK(Ca) of large conductance (BKCa), iberiotoxin, and small co
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15

McFerrin, Michael B., Kathryn L. Turner, Vishnu Anand Cuddapah, and Harald Sontheimer. "Differential role of IK and BK potassium channels as mediators of intrinsic and extrinsic apoptotic cell death." American Journal of Physiology-Cell Physiology 303, no. 10 (2012): C1070—C1078. http://dx.doi.org/10.1152/ajpcell.00040.2012.

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An important event during apoptosis is regulated cell condensation known as apoptotic volume decrease (AVD). Ion channels have emerged as essential regulators of this process mediating the release of K+ and Cl−, which together with osmotically obliged water, results in the condensation of cell volume. Using a Grade IV human glioblastoma cell line, we examined the contribution of calcium-activated K+ channels (KCa channels) to AVD after the addition of either staurosporine (Stsp) or TNF-α-related apoptosis-inducing ligand (TRAIL) to activate the intrinsic or extrinsic pathway of apoptosis, resp
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16

Essin, Kirill, Birgit Salanova, Ralph Kettritz, et al. "Large-conductance calcium-activated potassium channel activity is absent in human and mouse neutrophils and is not required for innate immunity." American Journal of Physiology-Cell Physiology 293, no. 1 (2007): C45—C54. http://dx.doi.org/10.1152/ajpcell.00450.2006.

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Large-conductance Ca2+-activated K+(BK) channels are reported to be essential for NADPH oxidase-dependent microbial killing and innate immunity in leukocytes. Using human peripheral blood and mouse bone marrow neutrophils, pharmacological targeting, and BK channel gene-deficient (BK−/−) mice, we stimulated NADPH oxidase activity with 12- O-tetradecanoylphorbol-13-acetate (PMA) and performed patch-clamp recordings on isolated neutrophils. Although PMA stimulated NADPH oxidase activity as assessed by O2−and H2O2production, our patch-clamp experiments failed to show PMA-activated BK channel curre
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17

Chang, Shaohua, Cristiano Mendes Gomes, Joseph A. Hypolite, et al. "Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein." American Journal of Physiology-Renal Physiology 298, no. 6 (2010): F1416—F1423. http://dx.doi.org/10.1152/ajprenal.00595.2009.

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Large-conductance voltage- and calcium-activated potassium (BK) channels have been shown to play a role in detrusor overactivity (DO). The goal of this study was to determine whether bladder outlet obstruction-induced DO is associated with downregulation of BK channels and whether BK channels affect myosin light chain 20 (MLC20) phosphorylation in detrusor smooth muscle (DSM). Partial bladder outlet obstruction (PBOO) was surgically induced in male New Zealand White rabbits. The rabbit PBOO model shows decreased voided volumes and increased voiding frequency. DSM from PBOO rabbits also show en
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18

Castillo, Karen, Gustavo F. Contreras, Amaury Pupo та ін. "Molecular mechanism underlying β1 regulation in voltage- and calcium-activated potassium (BK) channels". Proceedings of the National Academy of Sciences 112, № 15 (2015): 4809–14. http://dx.doi.org/10.1073/pnas.1504378112.

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Being activated by depolarizing voltages and increases in cytoplasmic Ca2+, voltage- and calcium-activated potassium (BK) channels and their modulatory β-subunits are able to dampen or stop excitatory stimuli in a wide range of cellular types, including both neuronal and nonneuronal tissues. Minimal alterations in BK channel function may contribute to the pathophysiology of several diseases, including hypertension, asthma, cancer, epilepsy, and diabetes. Several gating processes, allosterically coupled to each other, control BK channel activity and are potential targets for regulation by auxil
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Takács, Roland, Patrik Kovács, Rana Abdelsattar Ebeid, et al. "Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review." International Journal of Molecular Sciences 24, no. 7 (2023): 6796. http://dx.doi.org/10.3390/ijms24076796.

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Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the
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20

Hermann, Anton, Guzel Sitdikova, and Thomas Weiger. "Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels." Biomolecules 5, no. 3 (2015): 1870–911. http://dx.doi.org/10.3390/biom5031870.

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Salomao, L., G. Wark, W. P. Dubinsky, and S. G. Schultz. "Effect of trypsin on a Ca(2+)-activated K+ channel reconstituted into planar phospholipid bilayers." American Journal of Physiology-Cell Physiology 262, no. 4 (1992): C971—C974. http://dx.doi.org/10.1152/ajpcell.1992.262.4.c971.

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Exposure of the cytoplasmic side of calcium-activated, high (maxi)-conductance potassium [BK(Ca)] channels in basolateral membrane vesicles from rabbit colonocytes incorporated into planar phospholipid bilayers to trypsin rapidly reduces, but does not abolish, the sensitivity of this channel to activation by calcium without affecting its conductance or high selectivity for K+ over Cl-. The results of these studies also indicate that this BK(Ca) channel does not have intrinsic voltage-gating properties but that its voltage sensitivity is related to its ability to interact with calcium. This con
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Yan, Jiusheng, Qin Li, and Richard W. Aldrich. "Closed state-coupled C-type inactivation in BK channels." Proceedings of the National Academy of Sciences 113, no. 25 (2016): 6991–96. http://dx.doi.org/10.1073/pnas.1607584113.

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Ion channels regulate ion flow by opening and closing their pore gates. K+ channels commonly possess two pore gates, one at the intracellular end for fast channel activation/deactivation and the other at the selectivity filter for slow C-type inactivation/recovery. The large-conductance calcium-activated potassium (BK) channel lacks a classic intracellular bundle-crossing activation gate and normally show no C-type inactivation. We hypothesized that the BK channel’s activation gate may spatially overlap or coexist with the C-type inactivation gate at or near the selectivity filter. We induced
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23

Wang, Bin, Vladislav Bugay, Ling Ling, Hui-Hsui Chuang, David B. Jaffe та Robert Brenner. "Knockout of the BK β4-subunit promotes a functional coupling of BK channels and ryanodine receptors that mediate a fAHP-induced increase in excitability". Journal of Neurophysiology 116, № 2 (2016): 456–65. http://dx.doi.org/10.1152/jn.00857.2015.

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BK channels are large-conductance calcium- and voltage-activated potassium channels with diverse properties. Knockout of the accessory BK β4-subunit in hippocampus dentate gyrus granule neurons causes BK channels to change properties from slow-gated type II channels to fast-gated type I channels that sharpen the action potential, increase the fast afterhyperpolarization (fAHP) amplitude, and increase spike frequency. Here we studied the calcium channels that contribute to fast-gated BK channel activation and increased excitability of β4 knockout neurons. By using pharmacological blockers durin
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Shipston, Michael J. "Regulation of large conductance calcium- and voltage-activated potassium (BK) channels by S-palmitoylation." Biochemical Society Transactions 41, no. 1 (2013): 67–71. http://dx.doi.org/10.1042/bst20120226.

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BK (large conductance calcium- and voltage-activated potassium) channels are important determinants of physiological control in the nervous, endocrine and vascular systems with channel dysfunction associated with major disorders ranging from epilepsy to hypertension and obesity. Thus the mechanisms that control channel surface expression and/or activity are important determinants of their (patho)physiological function. BK channels are S-acylated (palmitoylated) at two distinct sites within the N- and C-terminus of the pore-forming α-subunit. Palmitoylation of the N-terminus controls channel tr
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S. S., Sambo. "THE ROLE OF LARGE CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS TO GASTROINTESTINAL MOTILITY." Archives of Pharmaceutical Sciences and Biotechnology Journal 4, no. 1 (2024): 101–13. https://doi.org/10.47514/apsbj.2024.4.1.010.

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Aim: This study is designed to investigate the role of large conductance calciumactivated (BK) channels in regulating gastrointestinal motility using mouse ileum strips in an organ bath preparation. Place and duration of study: This study was conducted in the School of Pharmacy and Biomedical Science at the University of Portsmouth, UK for a period of four months, from September 2015 to January 2016 Methodology: Experimental procedures to test viability of mouse ileum and response to compound NS19504 and Tetraethyl ammonium (TEA) were conducted using organ bath preparation containing Krebs sol
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Zhu, Yudan, Shuzhang Zhang, Yijun Feng, Qian Xiao, Jiwei Cheng, and Jie Tao. "The Yin and Yang of BK Channels in Epilepsy." CNS & Neurological Disorders - Drug Targets 17, no. 4 (2018): 272–79. http://dx.doi.org/10.2174/1871527317666180213142403.

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Background & Objective: The large conductance calcium-activated potassium (BK) channel, extensively distributed in the central nervous system (CNS), is considered as a vital player in the pathogenesis of epilepsy, with evidence implicating derangement of K+ as well as regulating action potential shape and duration. However, unlike other channels implicated in epilepsy whose function in neurons could clearly be labeled “excitatory” or “inhibitory”, the unique physiological behavior of the BK channel allows it to both augment and decrease the excitability of neurons. Thus, the role of BK in
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27

Hu, Song, Malgorzata Z. Labuda, Massimo Pandolfo, Greg G. Goss, Heather E. McDermid, and Declan W. Ali. "Variants of the KCNMB3 regulatory subunit of maxi BK channels affect channel inactivation." Physiological Genomics 15, no. 3 (2003): 191–98. http://dx.doi.org/10.1152/physiolgenomics.00110.2003.

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The steady-state and kinetic properties of the KCNMB3 regulatory subunits associated with calcium-activated potassium channels (BK channels) are presented. BK channels containing four sequence variants (V1–V4) in the four different isoforms of the β-subunit (β3a, β3b, β3c, and β3d) were expressed in Xenopus oocytes. Reconstituted BK channel inactivation ranged from none to around 90% inactivation. In particular, channels expressing the β3b-V4 variant displayed a right shift in the potassium current voltage-dependence of activation and inactivated to about 30% of the maximum conductance, compar
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Monreal, Marleni Reyes, Jessica Quintero Pérez, Miguel Felipe Pérez Escalera, Arturo Reyes Lazalde, and María Eugenia Pérez Bonilla. "Development of the L-type CaV / BK Complex Simulator (I): electrophysiological interaction." South Florida Journal of Development 2, no. 2 (2021): 1241–57. http://dx.doi.org/10.46932/sfjdv2n2-009.

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Complexes formed by voltage-activated calcium channels (CaV) and high-conductance potassium channels activated by Ca2+ (BK) have been studied in smooth muscle, secretory cells and in synaptic terminals, where they regulate muscle contraction, secretory activity, and neurotransmission. However, the complex formed by L- type CaV channels and BK in the soma has been poorly treated. Based on immunostaining studies showing the coexistence of these channels in the neuron soma, their possible interaction was theoretically studied. Two simulators based on the Hodgkin and Huxley formalism were develope
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Dickerson, Matthew T., Prasanna K. Dadi, Molly K. Altman та ін. "Glucose-mediated inhibition of calcium-activated potassium channels limits α-cell calcium influx and glucagon secretion". American Journal of Physiology-Endocrinology and Metabolism 316, № 4 (2019): E646—E659. http://dx.doi.org/10.1152/ajpendo.00342.2018.

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Pancreatic α-cells exhibit oscillations in cytosolic Ca2+ (Ca2+c), which control pulsatile glucagon (GCG) secretion. However, the mechanisms that modulate α-cell Ca2+c oscillations have not been elucidated. As β-cell Ca2+c oscillations are regulated in part by Ca2+-activated K+ (Kslow) currents, this work investigated the role of Kslow in α-cell Ca2+ handling and GCG secretion. α-Cells displayed Kslow currents that were dependent on Ca2+ influx through L- and P/Q-type voltage-dependent Ca2+ channels (VDCCs) as well as Ca2+ released from endoplasmic reticulum stores. α-Cell Kslow was decreased
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Li, Weiyan, and Richard W. Aldrich. "State-dependent Block of BK Channels by Synthesized Shaker Ball Peptides." Journal of General Physiology 128, no. 4 (2006): 423–41. http://dx.doi.org/10.1085/jgp.200609521.

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Crystal structures of potassium channels have strongly corroborated an earlier hypothetical picture based on functional studies, in which the channel gate was located on the cytoplasmic side of the pore. However, accessibility studies on several types of ligand-sensitive K+ channels have suggested that their activation gates may be located near or within the selectivity filter instead. It remains to be determined to what extent the physical location of the gate is conserved across the large K+ channel family. Direct evidence about the location of the gate in large conductance calcium-activated
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Wang, Bin, Brad S. Rothberg та Robert Brenner. "Mechanism of β4 Subunit Modulation of BK Channels". Journal of General Physiology 127, № 4 (2006): 449–65. http://dx.doi.org/10.1085/jgp.200509436.

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Large-conductance (BK-type) Ca2+-activated potassium channels are activated by membrane depolarization and cytoplasmic Ca2+. BK channels are expressed in a broad variety of cells and have a corresponding diversity in properties. Underlying much of the functional diversity is a family of four tissue-specific accessory subunits (β1–β4). Biophysical characterization has shown that the β4 subunit confers properties of the so-called “type II” BK channel isotypes seen in brain. These properties include slow gating kinetics and resistance to iberiotoxin and charybdotoxin blockade. In addition, the β4
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Dong, Ling, Yun-Min Zheng, Dee Van Riper, et al. "Functional and Molecular Evidence for Impairment of Calcium-Activated Potassium Channels in Type-1 Diabetic Cerebral Artery Smooth Muscle Cells." Journal of Cerebral Blood Flow & Metabolism 28, no. 2 (2007): 377–86. http://dx.doi.org/10.1038/sj.jcbfm.9600536.

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Cerebral vascular dysfunction and associated diseases often occur in type-1 diabetes, but the underlying mechanisms are largely unknown. In this study, we sought to determine whether big-conductance, Ca2+-activated K+ (BK) channels were impaired in vascular (cerebral artery) smooth muscle cells (CASMCs) from streptozotocin-induced type-1 diabetic mice using patch clamp, molecular biologic, and genetic approaches. Our data indicate that the frequency and amplitude of spontaneous transient outward currents (STOCs) are significantly decreased, whereas the activity of spontaneous Ca2+ sparks is in
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Ferrera, Loretta, Raffaella Barbieri, Cristiana Picco, et al. "TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase." International Journal of Molecular Sciences 22, no. 16 (2021): 8359. http://dx.doi.org/10.3390/ijms22168359.

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Tumor microenvironments are often characterized by an increase in oxidative stress levels. We studied the response to oxidative stimulation in human primary (IGR39) or metastatic (IGR37) cell lines obtained from the same patient, performing patch-clamp recordings, intracellular calcium ([Ca2+]i) imaging, and RT-qPCR gene expression analysis. In IGR39 cells, chloramine-T (Chl-T) activated large K+ currents (KROS) that were partially sensitive to tetraethylammonium (TEA). A large fraction of KROS was inhibited by paxilline—a specific inhibitor of large-conductance Ca2+-activated BK channels. The
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Brunton, Paula J., Matthias Sausbier, Georg Wietzorrek, et al. "Hypothalamic-Pituitary-Adrenal Axis Hyporesponsiveness to Restraint Stress in Mice Deficient for Large-Conductance Calcium- and Voltage-Activated Potassium (BK) Channels." Endocrinology 148, no. 11 (2007): 5496–506. http://dx.doi.org/10.1210/en.2007-0319.

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Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing ACTH from the anterior pituitary gland and glucocorticoids from the adrenal cortex. Stress also activates the sympathetic nervous system, evoking adrenaline release from the adrenal medulla. Large-conductance calcium- and voltage-activated potassium (BK) channels have been implicated in regulation of cellular excitability in these systems. Here, we examine the functional role of BK channels in HPA axis regulation in vivo using female mice genetically deficient (BK−/−) for the pore-forming subunits of BK channels. BK−/− p
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Orio, Patricio, Yolima Torres, Patricio Rojas та ін. "Structural Determinants for Functional Coupling Between the β and α Subunits in the Ca2+-activated K+ (BK) Channel". Journal of General Physiology 127, № 2 (2006): 191–204. http://dx.doi.org/10.1085/jgp.200509370.

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High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (β) subunits. The most remarkable effects of β1 and β2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by α and β1 or β2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of β1 but not β2. Here we reveal the molecular re
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Moldenhauer, Hans J., Katia K. Matychak, and Andrea L. Meredith. "Comparative gain-of-function effects of the KCNMA1-N999S mutation on human BK channel properties." Journal of Neurophysiology 123, no. 2 (2020): 560–70. http://dx.doi.org/10.1152/jn.00626.2019.

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KCNMA1, encoding the voltage- and calcium-activated potassium channel, has a pivotal role in brain physiology. Mutations in KCNMA1 are associated with epilepsy and/or dyskinesia (PNKD3). Two KCNMA1 mutations correlated with these phenotypes, D434G and N999S, were previously identified as producing gain-of-function (GOF) effects on BK channel activity. Three new patients have been reported harboring N999S, one carrying a second mutation, R1128W, but the effects of these mutations have not yet been reported under physiological K+ conditions or compared to D434G. In this study, we characterize N9
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Tao, Xiaoxiao, Mike T. Lin, Glyne U. Thorington, Sean M. Wilson, Lawrence D. Longo, and David A. Hessinger. "Long-term hypoxia increases calcium affinity of BK channels in ovine fetal and adult cerebral artery smooth muscle." American Journal of Physiology-Heart and Circulatory Physiology 308, no. 7 (2015): H707—H722. http://dx.doi.org/10.1152/ajpheart.00564.2014.

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Acclimatization to high-altitude, long-term hypoxia (LTH) reportedly alters cerebral artery contraction-relaxation responses associated with changes in K+ channel activity. We hypothesized that to maintain oxygenation during LTH, basilar arteries (BA) in the ovine adult and near-term fetus would show increased large-conductance Ca2+ activated potassium (BK) channel activity. We measured BK channel activity, expression, and cell surface distribution by use of patch-clamp electrophysiology, flow cytometry, and confocal microscopy, respectively, in myocytes from normoxic control and LTH adult and
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38

McClafferty, Heather, Hamish Runciman, and Michael J. Shipston. "Site-specific deacylation by ABHD17a controls BK channel splice variant activity." Journal of Biological Chemistry 295, no. 49 (2020): 16487–96. http://dx.doi.org/10.1074/jbc.ra120.015349.

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S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activ
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Gruslova, Aleksandra, Iurii Semenov та Bin Wang. "An extracellular domain of the accessory β1 subunit is required for modulating BK channel voltage sensor and gate". Journal of General Physiology 139, № 1 (2011): 57–67. http://dx.doi.org/10.1085/jgp.201110698.

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A family of tissue-specific auxiliary β subunits modulates large conductance voltage- and calcium-activated potassium (BK) channel gating properties to suit their diverse functions. Paradoxically, β subunits both promote BK channel activation through a stabilization of voltage sensor activation and reduce BK channel openings through an increased energetic barrier of the closed-to-open transition. The molecular determinants underlying β subunit function, including the dual gating effects, remain unknown. In this study, we report the first identification of a β1 functional domain consisting of Y
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40

Gonzalez-Perez, Vivian, Manu Ben Johny, Xiao-Ming Xia та Christopher J. Lingle. "Regulatory γ1 subunits defy symmetry in functional modulation of BK channels". Proceedings of the National Academy of Sciences 115, № 40 (2018): 9923–28. http://dx.doi.org/10.1073/pnas.1804560115.

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Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, β and γ, which help define the range of voltages over which BK channels in a given cell are activated, thereby defining physiological roles. A BK channe
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Vaca, L., A. Licea, and L. D. Possani. "Modulation of cell membrane potential in cultured vascular endothelium." American Journal of Physiology-Cell Physiology 270, no. 3 (1996): C819—C824. http://dx.doi.org/10.1152/ajpcell.1996.270.3.c819.

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The present study explores the role of different ionic conductances in the regulation of membrane potential under resting conditions and after bradykinin (BK) or thapsigargin (TG) stimulation of cultured bovine aortic endothelial cells. Under resting conditions, the cell membrane potential observed was -62+/- 5 mV. The main conductance under these conditions is an inwardly rectifying potassium (IRK) channel. Application of 50 nM BK induced a transient hyperpolarization to -87 +/- 4 mV followed by sustained depolarization to -35 +/- 5 mV. The transient hyperpolarization was eliminated by 1 micr
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Chambers, Jordan D., Joel C. Bornstein, Rachel M. Gwynne, Katerina Koussoulas, and Evan A. Thomas. "A detailed, conductance-based computer model of intrinsic sensory neurons of the gastrointestinal tract." American Journal of Physiology-Gastrointestinal and Liver Physiology 307, no. 5 (2014): G517—G532. http://dx.doi.org/10.1152/ajpgi.00228.2013.

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Intrinsic sensory neurons (ISNs) of the enteric nervous system respond to stimuli such as muscle tension, muscle length, distortion of the mucosa, and the chemical content in the lumen. ISNs form recurrent networks that probably drive many intestinal motor patterns and reflexes. ISNs express a large number of voltage- and calcium-gated ion channels, some of which are modified by inflammation or repeated physiological stimuli, but how interactions between different ionic currents in ISNs produce both normal and pathological behaviors in the intestine remains unclear. We constructed a model of I
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Liu, Guoxia, Sergey I. Zakharov, Lin Yang та ін. "Position and Role of the BK Channel α Subunit S0 Helix Inferred from Disulfide Crosslinking". Journal of General Physiology 131, № 6 (2008): 537–48. http://dx.doi.org/10.1085/jgp.200809968.

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The position and role of the unique N-terminal transmembrane (TM) helix, S0, in large-conductance, voltage- and calcium-activated potassium (BK) channels are undetermined. From the extents of intra-subunit, endogenous disulfide bond formation between cysteines substituted for the residues just outside the membrane domain, we infer that the extracellular flank of S0 is surrounded on three sides by the extracellular flanks of TM helices S1 and S2 and the four-residue extracellular loop between S3 and S4. Eight different double cysteine–substituted alphas, each with one cysteine in the S0 flank a
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Chung, Wen-Shuo, Jennifer L. Weissman, Jerry Farley та Heather A. Drummond. "βENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells". American Journal of Physiology-Renal Physiology 304, № 12 (2013): F1428—F1437. http://dx.doi.org/10.1152/ajprenal.00444.2012.

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Myogenic constrictor responses in small renal arteries and afferent arterioles are suppressed in mice with reduced levels of β-epithelial Na+ channel (βENaCm/m). The underlying mechanism is unclear. Decreased activity of voltage-gated calcium channels (VGCC) or mechanically gated ion channels and increased activity of large conductance calcium-activated potassium (BK) channels are a few possible mechanisms. The purpose of this study was to determine if VGCC, BK, or mechanically gated ion channel activity was altered in renal vascular smooth muscle cell (VSMC) from βENaCm/m mice. To address thi
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Li, Qin, Xin Guan, Karen Yen, Jiyuan Zhang та Jiusheng Yan. "The single transmembrane segment determines the modulatory function of the BK channel auxiliary γ subunit". Journal of General Physiology 147, № 4 (2016): 337–51. http://dx.doi.org/10.1085/jgp.201511551.

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The large-conductance, calcium-activated potassium (BK) channels consist of the pore-forming, voltage- and Ca2+-sensing α subunits (BKα) and the tissue-specific auxiliary β and γ subunits. The BK channel γ1 subunit is a leucine-rich repeat (LRR)–containing membrane protein that potently facilitates BK channel activation in many tissues and cell types through a vast shift in the voltage dependence of channel activation by ∼140 mV in the hyperpolarizing direction. In this study, we found that the single transmembrane (TM) segment together with its flanking charged residues is sufficient to fully
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Alqadah, Amel, Yi-Wen Hsieh, Rui Xiong, Bluma J. Lesch, Chieh Chang, and Chiou-Fen Chuang. "A universal transportin protein drives stochastic choice of olfactory neurons via specific nuclear import of a sox-2-activating factor." Proceedings of the National Academy of Sciences 116, no. 50 (2019): 25137–46. http://dx.doi.org/10.1073/pnas.1908168116.

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Stochastic neuronal cell fate choice involving notch-independent mechanisms is a poorly understood biological process. The Caenorhabditis elegans AWC olfactory neuron pair asymmetrically differentiates into the default AWCOFF and induced AWCON subtypes in a stochastic manner. Stochastic choice of the AWCON subtype is established using gap junctions and SLO BK potassium channels to repress a calcium-activated protein kinase pathway. However, it is unknown how the potassium channel-repressed calcium signaling is translated into the induction of the AWCON subtype. Here, we identify a detailed wor
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Orio, Patricio, та Ramon Latorre. "Differential Effects of β1 and β2 Subunits on BK Channel Activity". Journal of General Physiology 125, № 4 (2005): 395–411. http://dx.doi.org/10.1085/jgp.200409236.

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High conductance, calcium- and voltage-activated potassium (BK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (β) subunits. β1 and β2 subunits increase apparent channel calcium sensitivity. The β1 subunit also decreases the voltage sensitivity of the channel and the β2 subunit produces an N-type inactivation of BK currents. We further characterized the effects of the β1 and β2 subunits on the calcium and voltage sensitivity of the channel, analyzing the data in the context of an allosteric
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Gagov, Hristo, Irina Gribkova, Vladimir Serebryakov, and Rudolf Schubert. "Sodium Nitroprusside-Induced Activation of Vascular Smooth Muscle BK Channels Is Mediated by PKG Rather Than by a Direct Interaction with NO." International Journal of Molecular Sciences 23, no. 5 (2022): 2798. http://dx.doi.org/10.3390/ijms23052798.

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Nitric oxide (NO) is a powerful vasodilator in different vascular beds and NO-donors are widely used in clinical practice. Early data suggested that NO and NO-donors activate vascular smooth muscle high-conductance, calcium-activated potassium channels (BK channels). There exist two hypotheses explaining the effect of NO and NO-donors on BK channels—one stating that protein kinase G (PKG) mediates the effect of NO, and the other one stating that NO acts directly on the channel. Thus, the degree of contribution of PKG to the NO-induced activation of the BK channel is still not completely clear.
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Meredith, Andrea L., Steven W. Wiler, Brooke H. Miller, et al. "BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output." Nature Neuroscience 9, no. 8 (2006): 1041–49. http://dx.doi.org/10.1038/nn1740.

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Zhai, Xue, M. Dennis Leo, and Jonathan H. Jaggar. "Endothelin-1 Stimulates Vasoconstriction Through Rab11A Serine 177 Phosphorylation." Circulation Research 121, no. 6 (2017): 650–61. http://dx.doi.org/10.1161/circresaha.117.311102.

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Rationale: Large-conductance calcium-activated potassium channels (BK) are composed of pore-forming BKα and auxiliary β1 subunits in arterial smooth muscle cells (myocytes). Vasoconstrictors, including endothelin-1 (ET-1), inhibit myocyte BK channels, leading to contraction, but mechanisms involved are unclear. Recent evidence indicates that BKα is primarily plasma membrane localized, whereas the cellular location of β1 can be rapidly altered by Rab11A-positive recycling endosomes. Whether vasoconstrictors regulate the multisubunit composition of surface BK channels to stimulate contraction is
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