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https://www.readbyqxmd.com/read/29649319/unraveling-endothelin-1-induced-hypercontractility-of-human-pulmonary-artery-smooth-muscle-cells-from-patients-with-pulmonary-arterial-hypertension
#1
Jamie L Wilson, Rod Warburton, Linda Taylor, Deniz Toksoz, Nicholas Hill, Peter Polgar
Contraction of human pulmonary artery smooth muscle cells (HPASMC) isolated from pulmonary arterial hypertensive (PAH) and normal (non-PAH) subject lungs was determined and measured with real-time electrical impedance. Treatment of HPASMC with vasoactive peptides, endothelin-1 (ET-1) and bradykinin (BK) but not angiotensin II, induced a temporal decrease in the electrical impedance profile mirroring constrictive morphological change of the cells which typically was more robust in PAH as opposed to non-PAH cells...
2018: PloS One
https://www.readbyqxmd.com/read/29623857/the-large-conductance-calcium-and-voltage-activated-potassium-channel-bk-and-epilepsy-a-short-review
#2
Kai Zang, Yuwen Zhang, Jie Hu, Yun Wang
The large conductance calcium- and voltage-activated potassium channels (BK) are a kind of 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...
April 3, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29596016/chronic-interval-exercise-training-prevents-bk-ca-channel-mediated-coronary-vascular-dysfunction-in-aortic-banded-mini-swine
#3
T Dylan Olver, Jenna C Edwards, Brian S Ferguson, Jessica A Hiemstra, Pamela K Thorne, Michael A Hill, Maurice Harold Laughlin, Craig A Emter
Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this study was to determine the therapeutic efficacy of chronic interval exercise training (IT) on BKCa channel-mediated coronary vascular function in heart failure. We hypothesized chronic interval exercise training would attenuate pressure overload-induced impairments to coronary BKCa channel-mediated function. A translational large animal model with cardiac features of heart failure with preserved ejection fraction was used to test this hypothesis...
March 29, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29574460/the-unexpected-role-of-calcium-activated-potassium-channels-limitation-of-no-induced-arterial-relaxation
#4
Johannes Schmid, Bettina Müller, David Heppeler, Dina Gaynullina, Mario Kassmann, Hristo Gagov, Mitko Mladenov, Maik Gollasch, Rudolf Schubert
BACKGROUND: Multiple studies have shown that an NO-induced activation of vascular smooth muscle BK channels contributes to the NO-evoked dilation in many blood vessels. In vivo, NO is released continuously. NO attenuates vessel constrictions and, therefore, exerts an anticontractile effect. It is unknown whether the anticontractile effect of continuously present NO is mediated by BK channels. METHODS AND RESULTS: This study tested the hypothesis that BK channels mediate the vasodilatory effect of continuously present NO...
March 24, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29545539/solution-structure-of-extracellular-loop-of-human-%C3%AE-4-subunit-of-bk-channel-and-its-biological-implication-on-chtx-sensitivity
#5
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
https://www.readbyqxmd.com/read/29545233/expanding-the-phenotype-of-homozygous-kcnma1-mutations-dyskinesia-epilepsy-intellectual-disability-cerebellar-and-corticospinal-tract-atrophy
#6
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
https://www.readbyqxmd.com/read/29540546/regulation-of-nociceptive-glutamatergic-signaling-by-presynaptic-kv3-4-channels-in-the-rat-spinal-dorsal-horn
#7
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
https://www.readbyqxmd.com/read/29537866/negative-regulation-of-cellular-ca-2-mobilization-by-ryanodine-receptor-type-3-in-mouse-mesenteric-artery-smooth-muscle
#8
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
https://www.readbyqxmd.com/read/29530986/cereblon-maintains-synaptic-and-cognitive-function-by-regulating-bk-channel
#9
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
https://www.readbyqxmd.com/read/29523816/purkinje-cell-bkchannel-ablation-induces-abnormal-rhythm-in-deep-cerebellar-nuclei-and-prevents-ltd
#10
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
https://www.readbyqxmd.com/read/29511121/a-role-for-corticotropin-releasing-factor-signaling-in-the-lateral-habenula-and-its-modulation-by-early-life-stress
#11
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
https://www.readbyqxmd.com/read/29508439/dopamine-d1-receptor-mediated-upregulation-of-bk-ca-currents-modifies-m%C3%A3-ller-cell-gliosis-in-a-rat-chronic-ocular-hypertension-model
#12
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
https://www.readbyqxmd.com/read/29488290/inhibition-of-zero-bk-by-pkc-is-involved-in-carbachol-induced-enhancement-of-rat-colon-smooth-muscle-motility
#13
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
https://www.readbyqxmd.com/read/29486465/chronic-prenatal-hypoxia-down-regulated-bk-channel-%C3%AE-1-subunits-in-mesenteric-artery-smooth-muscle-cells-of-the-offspring
#14
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
https://www.readbyqxmd.com/read/29466724/bk-potassium-channels-suppress-cav%C3%AE-2%C3%AE-subunit-function-to-reduce-inflammatory-and-neuropathic-pain
#15
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
https://www.readbyqxmd.com/read/29466671/lipopolysaccharide-stimulates-bk-channel-activity-in-bladder-umbrella-cells
#16
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
https://www.readbyqxmd.com/read/29453198/targeting-kca1-1-channels-with-a-scorpion-venom-peptide-for-the-therapy-of-rat-models-of-rheumatoid-arthritis
#17
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
https://www.readbyqxmd.com/read/29438488/cardioprotection-by-ischemic-postconditioning-and-cgmp-elevating-agents-involves-cardiomyocyte-nitric-oxide-sensitive-guanylyl-cyclase
#18
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
https://www.readbyqxmd.com/read/29437015/the-yin-and-yang-of-bk-channels-in-epilepsy
#19
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
https://www.readbyqxmd.com/read/29422008/lysosomal-potassium-channels-potential-roles-in-lysosomal-function-and-neurodegenerative-diseases
#20
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
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