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BK channel

Jay S Naik, Jessica M Osmond, Benjimen R Walker, Nancy L Kanagy
Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtansferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large conductance Ca(2+)-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
Yoshiaki Suzuki, Susumu Ohya, Hisao Yamamura, Wayne R Giles, Yuji Imaizumi
Large-conductance Ca(2+)-activated K(+) (BK) channels play essential roles in both excitable and non-excitable cells. For example, in chondrocytes, agonist-induced Ca(2+) release from intracellular store activates BK channels, and this hyperpolarizes these cells, augments Ca(2+) entry, and forms a positive feed-back mechanism for Ca(2+) signaling and stimulation-secretion coupling. In the present study, functional roles of a newly identified splice variant in the BK channel α subunit (BKαΔe2) were examined in a human chondrocyte cell line, OUMS-27, and in a HEK293 expression system...
October 7, 2016: Journal of Biological Chemistry
Zhenzhen Yan, Bin Hu, Zhigang Huang, Ling Zhong, Xiying Guo, Anxi Weng, Feng Xiao, Wenping Zeng, Yan Zhang, Jiuping Ding, Panpan Hou
Large-conductance Ca2+- and voltage-activated potassium (BK) channels are widely expressed in tissues. As a voltage and calcium sensor, BK channels play significant roles in regulating the action potential frequency, neurotransmitter release, and smooth muscle contraction. After associating with the auxiliary β2 subunit, mammalian BK(β2) channels (mouse or human Slo1/β2) exhibit enhanced activation and complete inactivation. However, how the β2 subunit modulates the Drosophila Slo1 channel remains elusive...
2016: PloS One
Manuel Sánchez, Lorena Suárez, Begoña Cantabrana, Javier Bordallo
Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca(2+) associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca(2+) and noninactivating K(+) currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH3...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Cristina Velázquez-Marrero, Alexandra Burgos, José O García, Stephanie Palacio, Héctor G Marrero, Alexandra Bernardo, Juliana Pérez-Laspiur, Marla Rivera-Oliver, Garrett Seale, Steven N Treistman
: It has been suggested that drug tolerance represents a form of learning and memory, but this has not been experimentally established at the molecular level. We show that a component of alcohol molecular tolerance (channel internalization) from rat hippocampal neurons requires protein synthesis, in common with other forms of learning and memory. We identify β-catenin as a primary necessary protein. Alcohol increases β-catenin, and blocking accumulation of β-catenin blocks alcohol-induced internalization in these neurons...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Kaivan Khavandi, Rachael L Baylie, Sarah A Sugden, Majid Ahmed, Viktoria Csato, Philip Eaton, David C Hill-Eubanks, Adrian D Bonev, Mark T Nelson, Adam S Greenstein
Activation of Ca(2+)-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca(2+) signals (Ca(2+) sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues...
October 11, 2016: Science Signaling
Wenqing Shi, Yuhan Zeng, Lushan Zhou, Yucheng Xiao, Theodore R Cummins, Lane A Baker
We describe dual-barrel ion channel probes (ICPs), which consist of an open barrel and a barrel with a membrane patch directly excised from a donor cell. When incorporated with scanning ion conductance microscopy (SICM), the open barrel (SICM barrel) serves to measure the distance-dependent ion current for non-invasive imaging and positioning of the probe in the same fashion of traditional SICM. The second barrel with the membrane patch supports ion channels of interest and was used to investigate ion channel activities...
September 16, 2016: Faraday Discussions
Min Lin, Danielle Sambo, Habibeh Khoshbouei
: Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zhi-Gang Huang, Hao-Wen Liu, Zhen-Zhen Yan, Sheng Wang, Lu-Yang Wang, Jiu-Ping Ding
Large-conductance Ca(2+)- and voltage- activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and four types of auxiliary β subunits or just a pore-forming α subunit. Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels. Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that three sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119)...
October 3, 2016: Channels
Xi Zoë Zhong, Xue Sun, Qi Cao, Gaofeng Dong, Raphael Schiffmann, Xian-Ping Dong
Efficient lysosomal Ca(2+) release plays an essential role in lysosomal trafficking. We have recently shown that lysosomal big conductance Ca(2+)-activated potassium (BK) channel forms a physical and functional coupling with the lysosomal Ca(2+) release channel Transient Receptor Potential Mucolipin-1 (TRPML1). BK and TRPML1 forms a positive feedback loop to facilitate lysosomal Ca(2+) release and subsequent lysosome membrane trafficking. However, it is unclear whether the positive feedback mechanism is common for other lysosomal storage diseases (LSDs) and whether BK channel agonists rescue abnormal lysosomal storage in LSDs...
September 27, 2016: Scientific Reports
Tobias Bock, Greg J Stuart
Large conductance calcium-activated potassium channels (or BK channels) fulfil a multitude of roles in the central nervous system. At the soma of many neuronal cell types they control the speed of action potential (AP) repolarization and therefore they can have an impact on neuronal excitability. Due to their presence in nerve terminals they also regulate transmitter release. BK channels have also been shown to be present in the dendrites of some neurons where they can regulate the magnitude and duration of dendritic spikes...
2016: Frontiers in Cellular Neuroscience
Anusha Mishra
Astrocytes are the most common glial cells in the brain with fine processes and endfeet that intimately contact both neuronal synapses and the cerebral vasculature. They play an important role in mediating neurovascular coupling (NVC) via several astrocytic Ca(2+) -dependent signalling pathways such as K(+) release through BK channels, and the production and release of arachidonic acid metabolites. They are also involved in maintaining the resting tone of the cerebral vessels by releasing ATP and COX-1 derivatives...
September 13, 2016: Journal of Physiology
Matthew D Perry, Vazhaikkurichi M Rajendran, Kenneth MacLennan, Geoffrey I Sandle
Rat proximal and distal colon are net K(+) secretory and net K(+) absorptive epithelia, respectively. Chronic dietary K(+) loading increases net K(+) secretion in the proximal colon, and transforms net K(+) absorption to net K(+) secretion in the distal colon, but changes in apical K(+) channel expression are unclear. We evaluated expression/activity of apical K(+) (BK) channels in surface colonocytes in proximal and distal colon of control and K(+) loaded animals using patch-clamp recording, immunohistochemistry and western blot analyses...
September 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Paolo Rosa, Luigi Sforna, Silvia Carlomagno, Giorgio Mangino, Massimo Miscusi, Mauro Pessia, Fabio Franciolini, Antonella Calogero, Luigi Catacuzzeno
Glioblastomas (GBMs) are brain tumors characterized by diffuse invasion of cancer cells into the healthy brain parenchyma, and establishment of secondary foci. GBM cells abundantly express large-conductance, calcium-activated potassium (BK) channels that are thought to promote cell invasion. Recent evidence suggests that the GBM high invasive potential mainly originates from a pool of stem-like cells, but the expression and function of BK channels in this cell subpopulation have not been studied. We investigated the expression of BK channels in GBM stem-like cells using electrophysiological and immunochemical techniques, and assessed their involvement in the migratory process of this important cell subpopulation...
September 8, 2016: Journal of Cellular Physiology
Julia Illison, Lijun Tian, Heather McClafferty, Martin Werno, Luke H Chamberlain, Veronika Leiss, Antonia Sassmann, Stefan Offermanns, Peter Ruth, Michael J Shipston, Robert Lukowski
Elevated adipose tissue expression of the Ca(2+)- and voltage-activated K(+) (BK) channel was identified in morbidly obese men carrying a BK gene variant supporting the hypothesis that K(+) channels affect metabolic responses of fat cells to nutrients. To establish the role of endogenous BKs for fat cell maturation, storage of excess dietary fat and body-weight (BW) gain we studied a gene-targeted mouse model with a global ablation of the BK channel (BK(L1/L1)) and adipocyte-specific BK-deficient (adipoqBK(L1/L2)) mice...
September 7, 2016: Diabetes
Kiril L Hristov, Shankar P Parajuli, Aaron Provence, Georgi V Petkov
In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability...
September 7, 2016: American Journal of Physiology. Renal Physiology
Tong Lu, Bin Jiang, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice...
September 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Shivantika Bisen, Olga Seleverstov, Jitendra Belani, Scott Rychnovsky, Alex M Dopico, Anna N Bukiya
Alcohol (ethanol) at concentrations reached in blood following moderate to heavy drinking (30-80mM) reduces cerebral artery diameter via inhibition of voltage- and calcium-gated potassium channels of large conductance (BK) in cerebral artery smooth muscle. These channels consist of channel-forming α and regulatory β1 subunits. A high-cholesterol diet protects against ethanol-induced constriction via accumulation of cholesterol within the vasculature. The molecular mechanisms of this protection remain unknown...
August 24, 2016: Biochimica et Biophysica Acta
Myriam Fezai, Musaab Ahmed, Zohreh Hosseinzadeh, Florian Lang
BACKGROUND/AIMS: The pleotropic functions of the large conductance Ca2+-activated K+ channels (maxi K+ channel or BK channels) include regulation of neuronal excitation and cell volume. Kinases participating in those functions include the glycogen synthase kinase GSK3 ß which is under negative control of protein kinase B (PKB/Akt). GSK3ß is inhibited by the antidepressant Lithium. The present study thus explored whether GSK3ß modifies the activity of BK channels. METHODS: cRNA encoding the Ca2+ insensitive BK channel mutant BKM513I+Δ899-903 was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type GSK3ß, inactive K85RGSK3ß, or wild-type GSK3ß with wild-type PKB...
2016: Cellular Physiology and Biochemistry
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