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Bk channels

Yanting Wang, Wenxian Lan, Zhenzhen Yan, Jing Gao, Xinlian Liu, Sheng Wang, Xiying Guo, Chunxi Wang, Hu Zhou, Jiuping Ding, Chunyang Cao
Large-conductance Ca2+ - and voltage-dependent K+ (BK) channels display diverse biological functions while their pore-forming α subunit is coded by a single Slo1 gene. The variety of BK channels is correlated with the effects of BKα coexpression with auxiliary β (β1-β4) subunits, as well as newly defined γ subunits. Charybdotoxin (ChTX) blocks BK channel through physically occluding the K+ -conduction pore. Human brain enriched β4 subunit (hβ4) alters the conductance-voltage curve, slows activation and deactivation time courses of BK channels...
March 15, 2018: Scientific Reports
Gözde Yeşil, Ayşe Aralaşmak, Enes Akyüz, Dilara İçağasıoğlu, Türkan Uygur Şahin, Yavuz Bayram
BACKGROUND: The KCNMA1 gene encodes the α-subunit of the large conductance, voltage and calcium-sensitive potassium channel (BK channels) which plays an important role in neuronal excitability. Heterozygous mutations in KCNMA1 were firstly described in a large family with generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. Recently, homozygous KCNMA1 mutations were reported to cause a phenotype of cerebellar atrophy, developmental delay and seizures. CASE REPORT: Herein; we report a patient with a novel homozygous truncating mutation in KCNMA1 (p...
March 16, 2018: Balkan Medical Journal
Tanziyah Muqeem, Biswarup Ghosh, Vitor Pinto, Angelo C Lepore, Manuel Covarrubias
Presynaptic voltage-gated K+ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Katsuhito Matsuki, Daiki Kato, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Physiological functions of type 3 ryanodine receptors (RyR3) in smooth muscle (SM) tissues are not well understood, in spite of their wide expression. However, the short isoform of RyR3 is known to be a dominant negative variant (DN-RyR3), which may negatively regulate functions of both RyR2 and full length (FL)-RyR3 by forming hetero-tetramers. Here, functional roles of RyR3 in the regulation of Ca2+ signaling in mesenteric artery SM cells (MASMCs) were examined using RyR3 homozygous knockout mice (RyR3-/- )...
March 14, 2018: American Journal of Physiology. Cell Physiology
Tae-Yong Choi, Seung-Hyun Lee, Yoon-Jung Kim, Jae Ryul Bae, Kwang Min Lee, Youhwa Jo, Soo-Jeong Kim, A-Ram Lee, Sekyu Choi, La-Mee Choi, Sunhoe Bang, Mi-Ryoung Song, Jongkyeong Chung, Kyung Jin Lee, Sung Hyun Kim, Chul-Seung Park, Se-Young Choi
Mutations in the cereblon ( CRBN ) gene cause human intellectual disability, one of the most common cognitive disorders. However, the molecular mechanisms of CRBN -related intellectual disability remain poorly understood. We investigated the role of CRBN in synaptic function and animal behavior using male mouse and Drosophila models. Crbn knockout (KO) mice showed normal brain and spine morphology as well as intact synaptic plasticity; however, they also exhibited decreases in synaptic transmission and presynaptic release probability exclusively in excitatory synapses...
March 12, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Guy Cheron, Javier Márquez-Ruiz, Julian Cheron, Cynthia Prigogine, Claudia Ammann, Robert Lukowski, Peter Ruth, Bernard Dan
Purkinje cells (PC) control deep cerebellar nuclei (DCN), which in turn inhibit inferior olive nucleus, closing a positive feedback loop via climbing fibers. PC highly express potassium BK channels but their contribution to the olivo-cerebellar loop is not clear. Using multiple-unit recordings in alert mice we found in that selective deletion of BK channels in PC induces a decrease in their simple spike firing with a beta-range bursting pattern and fast intraburst frequency (~200 Hz). To determine the impact of this abnormal rhythm on the olivo-cerebellar loop we analyzed simultaneous rhythmicity in different cerebellar structures...
March 9, 2018: Scientific Reports
Michael E Authement, Ludovic D Langlois, Ryan D Shepard, Caroline A Browne, Irwin Lucki, Haifa Kassis, Fereshteh S Nugent
Centrally released corticotropin-releasing factor or hormone (extrahypothalamic CRF or CRH) in the brain is involved in the behavioral and emotional responses to stress. The lateral habenula (LHb) is an epithalamic brain region involved in value-based decision-making and stress evasion. Through its inhibition of dopamine-mediated reward circuitry, the increased activity of the LHb is associated with addiction, depression, schizophrenia, and behavioral disorders. We found that extrahypothalamic CRF neurotransmission increased neuronal excitability in the LHb...
March 6, 2018: Science Signaling
Hang-Jing Wu, Xue-Yan Li, Wen-Jing Qian, Qian Li, Shu-Yue Wang, Min Ji, Yuan-Yuan Ma, Feng Gao, Xing-Huai Sun, Xin Wang, Yanying Miao, Xiong-Li Yang, Zhongfeng Wang
Müller cell gliosis is a common response in many retinal pathological conditions. We previously demonstrated that downregulation of Kir channels contributes to Müller cell gliosis in a rat chronic ocular hypertension (COH) model. Here, the possible involvement of outward K+ currents in Müller cell gliosis was investigated. Outward K+ current densities in Müller cells isolated from COH rats, as compared with those in normal rats, showed a significant increase, which was mainly contributed by large-conductance Ca2+ -activated K+ (BKCa ) channels...
March 6, 2018: Glia
F Xin, H Huang, P Liu, J Ren, S Zhang, Y Cheng, W Wang
BACKGROUND: Muscarinic acetylcholine receptor (mAChR) activation is an important factor to enhance the motility of gastrointestinal (GI) smooth muscle. Large conductance Ca2+ -activated potassium (BK) channels are widely expressed in GI smooth muscle. Roles of BK in carbachol (a mAChR agonist) induced enhancement of GI motility and the molecular mechanisms remains unknown and were investigated in this study. METHODS: Colonic smooth muscle (CSM) strip was perfused to record motility in vitro...
February 28, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Bailin Liu, Yanping Liu, Ruixiu Shi, Xueqin Feng, Xiang Li, Wenna Zhang, Jue Wu, Na Li, Xiuwen Zhou, Miao Sun, Zhice Xu
BACKGROUND/AIMS: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca2+-activated K+ (BK) channels in offspring mesenteric arteries following prenatal hypoxia. METHODS: Pregnant rats were exposed to normoxic control (21% O2, Con) or hypoxic (10.5% O2, Hy) conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR...
February 21, 2018: Cellular Physiology and Biochemistry
Fang-Xiong Zhang, Vinicius M Gadotti, Ivana A Souza, Lina Chen, Gerald W Zamponi
Cavα2δ subunits contribute to the cell-surface expression of Cav2 calcium channels. Upregulation of Cavα2δ-1 in dorsal root ganglion neurons occurs after nerve injury and results in an increased synaptic abundance of Cav2.2 channels in the spinal dorsal horn, thus enhancing the transmission of pain signals. Here, we report that large conductance calcium-activated potassium (BK) channels interact with the Cavα2δ subunit. Coexpression of BK channels with the Cav2 calcium channels reduces their cell-surface expression and whole-cell current density by competing the Cavα2δ subunit away from the Cav2 complex...
February 20, 2018: Cell Reports
Ming Lu, Jian-Ri Li, Lery Alvarez-Lugo, Yan Li, Shan Yu, Xuanhao Li, Benkang Shi, Toby C Chai
Bladder urothelium plays an active role in response to bacterial infection. There is little known about the electrophysiological activity in urothelial cells in this process. We used a non-enzymatic method to isolate bladder urothelial tissue and to patch clamp umbrella cells in situ. A 200pS conductance potassium (K+ ) channel was detected from female C57BL6 mice. Of 58 total patches, 17.2% patches displayed the 200pS K+ conductance channel. This K+ conductance channel showed Ca2+ sensitivity and voltage dependence...
February 21, 2018: American Journal of Physiology. Cell Physiology
Mark R Tanner, Michael W Pennington, Brayden H Chamberlain, Redwan Huq, Elizabeth J Gehrmann, Teresina Laragione, Percio S Gulko, Christine Beeton
Fibroblast-like synoviocytes (FLS) are a key cell-type involved in rheumatoid arthritis (RA) progression. We previously identified the KCa1.1 potassium channel (Maxi-K, BK, Slo 1, KCNMA1) as a regulator of FLS and that KCa1.1 inhibition reduces disease severity in RA animal models. However, systemic KCa1.1 block causes multiple side effects and in this study, we aimed to determine whether the KCa1.1 β1-3-specific venom peptide blocker iberiotoxin (IbTX) reduces disease severity in animal models of RA without inducing major side effects...
February 16, 2018: Journal of Pharmacology and Experimental Therapeutics
Sandra Frankenreiter, Dieter Groneberg, Anna Kuret, Thomas Krieg, Peter Ruth, Andreas Friebe, Robert Lukowski
Aims: It has been suggested that the nitric oxide-sensitive guanylyl cyclase (NO-GC)/cGMP-dependent signaling pathway affords protection against cardiac damage during acute myocardial infarction (AMI). It is, however, not clear whether the NO-GC/cGMP system confers its favorable effects through a mechanism located in cardiomyocytes (CMs). The aim of this study was to evaluate the infarct-limiting effects of the endogenous NO-GC in CMs in vivo. Methods and Results: Ischemia/reperfusion (I/R) injury was evaluated in mice with a cardiomyocyte-specific deletion of NO-GC (CM NO-GC KO) and in control siblings (CM NO-GC CTR) subjected to an in vivo model of AMI...
February 9, 2018: Cardiovascular Research
Yudan Zhu, Shuzhang Zhang, Yijun Feng, Qian Xiao, Jiwei Cheng, Jie Tao
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...
February 13, 2018: CNS & Neurological Disorders Drug Targets
Xinghua Feng, Zhuangzhuang Zhao, Qian Li, Zhiyong Tan
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...
February 1, 2018: CNS & Neurological Disorders Drug Targets
Guohui Zhang, Jianmin Cui
The Xenopus oocyte expression system is ideal for electrophysiological characterization of voltage-dependent and ligand-dependent ion channels because of its relatively low background of endogenous channels and the large size of the cell. Here, we present a protocol to study voltage- and ligand-dependent activation of ion channels expressed in Xenopus oocytes using patch-clamp techniques designed to control both the membrane voltage and the intracellular solution. In this protocol, the large conductance voltage- and Ca2+-activated K+ (BK) channel is studied as an example...
January 30, 2018: Cold Spring Harbor Protocols
Jay S Naik, Benjimen R Walker
Following chronic hypoxia (CH), the systemic vasculature exhibits blunted vasoconstriction due to endothelial-dependent hyperpolarization (EDH). Previous data demonstrate that subsequent to CH, EDH-mediated vasodilation switches from a reliance on SKca and IKca channels to activation of the endothelial BKca channels (eBK). The mechanism by which endothelial cell stimulation activates eBK channels following CH is not known. We hypothesized that following CH, EDH-dependent vasodilation involves a TRPV4-dependent activation of eBK channels...
January 29, 2018: Pflügers Archiv: European Journal of Physiology
Yanrong Zhu, Peng Ye, Shao-Liang Chen, Dai-Min Zhang
The large conductance Ca2+-activated potassium channels, the BK channels, is widely expressed in various tissues and activated in a Ca2+- and voltage-dependent manner. The activation of BK channels hyperpolarizes vascular smooth muscle cell membrane potential, resulting in vasodilation. Under pathophysiological conditions, such as diabetes mellitus and hypertension, impaired BK channel function exacerbates vascular vasodilation and leads to organ ischemia. The vascular BK channel is composed of 4 pore-forming subunits, BK-α together with 4 auxiliary subunits: β1 subunits (BK-β1) or γ1 subunits (BK-γ1)...
January 23, 2018: Metabolism: Clinical and Experimental
Ying-Ying Zhang, Xue Han, Ye Liu, Jian Chen, Lei Hua, Qian Ma, Yang-Yu-Xin Huang, Qiong-Yao Tang, Zhe Zhang
LRRC55 (leucine-rich repeat-containing protein 55) protein is an auxiliary γ subunit of BK (Big conductance potassium channel) channels, which leftward shifts GVs of BK channels around 50 mV in the absence of cytosolic Ca2+. LRRC55 protein is also the only γ subunit of BK channels that is expressed in mammalian nervous system. However, the expression pattern of LRRC55 gene in adult mammalian brain remains elusive. In this study, we investigated the distribution of LRRC55 mRNA in the adult mouse brain by using in situ hybridization...
2018: PloS One
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