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BK channel

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https://www.readbyqxmd.com/read/29453198/targeting-kca1-1-channels-with-a-scorpion-venom-peptide-for-the-therapy-of-rat-models-of-rheumatoid-arthritis
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/29382809/patch-clamp-and-perfusion-techniques-to-study-ion-channels-expressed-in-xenopus-oocytes
#5
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
https://www.readbyqxmd.com/read/29380056/endothelial-dependent-dilation-following-chronic-hypoxia-involves-trpv4-mediated-activation-of-endothelial-bk-channels
#6
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
https://www.readbyqxmd.com/read/29373813/functional-regulation-of-large-conductance-ca2-activated-k-channels-in-vascular-diseases
#7
REVIEW
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
https://www.readbyqxmd.com/read/29370300/-mrna-expression-of-lrrc55-protein-leucine-rich-repeat-containing-protein-55-in-the-adult-mouse-brain
#8
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
https://www.readbyqxmd.com/read/29370161/crl4-antagonizes-scffbxo7-mediated-turnover-of-cereblon-and-bk-channel-to-regulate-learning-and-memory
#9
Tianyu Song, Shenghui Liang, Jiye Liu, Tingyue Zhang, Yifei Yin, Chenlu Geng, Shaobing Gao, Yan Feng, Hao Xu, Dongqing Guo, Amanda Roberts, Yuchun Gu, Yong Cang
Intellectual disability (ID), one of the most common human developmental disorders, can be caused by genetic mutations in Cullin 4B (Cul4B) and cereblon (CRBN). CRBN is a substrate receptor for the Cul4A/B-DDB1 ubiquitin ligase (CRL4) and can target voltage- and calcium-activated BK channel for ER retention. Here we report that ID-associated CRL4CRBN mutations abolish the interaction of the BK channel with CRL4, and redirect the BK channel to the SCFFbxo7 ubiquitin ligase for proteasomal degradation. Glioma cell lines harbouring CRBN mutations record density-dependent decrease of BK currents, which can be restored by blocking Cullin ubiquitin ligase activity...
January 25, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29370072/mitochondrial-bk-channel-openers-cgs7181-and-cgs7184-exhibit-cytotoxic-properties
#10
Bartłomiej Augustynek, Piotr Koprowski, Daria Rotko, Wolfram S Kunz, Adam Szewczyk, Bogusz Kulawiak
Potassium channel openers (KCOs) have been shown to play a role in cytoprotection through the activation of mitochondrial potassium channels. Recently, in several reports, a number of data has been described as off-target actions for KCOs. In the present study, we investigated the effects of BKCa channel openers CGS7181, CGS7184, NS1619, and NS004 in neuronal cells. For the purpose of this research, we used a rat brain, the mouse hippocampal HT22 cells, and the human astrocytoma U-87 MG cell line. We showed that CGS7184 activated the mitochondrial BKCa (mitoBKCa) channel in single-channel recordings performed on astrocytoma mitoplasts...
January 25, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29357444/renal-potassium-handling-in-rats-with-subtotal-nephrectomy-modeling-and-analysis
#11
Anita T Layton, Aurélie Edwards, Volker Vallon
We sought to decipher the mechanisms underlying the kidney's response to changes in K+ load and intake, under physiological and pathophysiological conditions. To accomplish that goal, we applied a published computational model of epithelial transport along rat nephrons in a \Red{sham}, uninephrectomized (UNX), and 5/6-nephrectomized (5/6-NX) \Red{rats that also considers adaptations in GFR and tubular growth}. Model simulations \Red{of an acute K+ load} indicate that elevated expression levels and activities of Na+/K+-ATPase, epithelial sodium channels (ENaC), large conductance Ca2+-activated K+ channels (BK), and renal outer medullary K+ channels (ROMK), together with downregulation of sodium-chloride cotransporters (NCC), increase K+ secretion along the connecting tubule, resulting in a > 6-fold increase in urinary K+ excretion in \Red{sham rats}, which substantially exceeds the filtered K+ load...
December 13, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29352074/aldosterone-sgk1-and-ion-channels-in-the-kidney
#12
REVIEW
William C Valinsky, Rhian M Touyz, Alvin Shrier
Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na+, K+, and Mg2+ dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na+ (ENaC), K+ (ROMK/BK), Ca2+ (TRPV4/5/6), Mg2+ (TRPM7/6), and Cl- (ClC-K, CFTR)...
January 31, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29348160/up-all-night-bk-channels-circadian-dance-with-different-calcium-sources
#13
Caitlin Sedwick
JGP study explores diurnal changes in calcium sources governing BK activity in the SCN.
January 18, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29330545/de-novo-bk-channel-variant-causes-epilepsy-by-affecting-voltage-gating-but-not-ca2-sensitivity
#14
Xia Li, Sibylle Poschmann, Qiuyun Chen, Walid Fazeli, Nelly Jouayed Oundjian, Francesca M Snoeijen-Schouwenaars, Oliver Fricke, Erik-Jan Kamsteeg, Marjolein Willemsen, Qing Kenneth Wang
Epilepsy is one of the most common neurological diseases and it causes profound morbidity and mortality. We identified the first de novo variant in KCNMA1 (c.2984 A > G (p.(N995S)))-encoding the BK channel-that causes epilepsy, but not paroxysmal dyskinesia, in two independent families. The c.2984 A > G (p.(N995S)) variant markedly increased the macroscopic potassium current by increasing both the channel open probability and channel open dwell time. The c.2984 A > G (p.(N995S)) variant did not affect the calcium sensitivity of the channel...
January 12, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29325119/mir-96-is-required-for-normal-development-of-the-auditory-hindbrain
#15
Tina Schlüter, Christina Berger, Elena Rosengauer, Pascal Fieth, Constanze Krohs, Kathy Ushakov, Karen P Steel, Karen B Avraham, Alexander Hartmann, Felix Felmy, Hans Gerd Nothwang
The peripheral deafness gene Mir96 is expressed in both the cochlea and central auditory circuits. To investigate whether it plays a role in the auditory system beyond the cochlea, we characterized homozygous Dmdo/Dmdo mice with a point mutation in miR-96. Anatomical analysis demonstrated a significant decrease in volume of auditory nuclei in Dmdo/Dmdo mice. This decrease resulted from decreased cell size. Non-auditory structures in the brainstem of Dmdo/Dmdo mice or auditory nuclei of the congenital deaf Cldn14-/- mice revealed no such differences...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29323236/molecular-determinants-of-ca2-sensitivity-at-the-intersubunit-interface-of-the-bk-channel-gating-ring
#16
Qin Li, Yingxin Li, Hua Wei, Hao-Min Pan, Alexandre G Vouga, Brad S Rothberg, Yunkun Wu, Jiusheng Yan
The large-conductance calcium-activated K+ (BK) channel contains two intracellular tandem Ca2+-sensing RCK domains (RCK1 and RCK2), which tetramerize into a Ca2+ gating ring that regulates channel opening by conformational expansion in response to Ca2+ binding. Interestingly, the gating ring's intersubunit assembly interface harbors the RCK2 Ca2+-binding site, known as the Ca2+ bowl. The gating ring's assembly interface is made in part by intersubunit coordination of a Ca2+ ion between the Ca2+ bowl and an RCK1 Asn residue, N449, and by apparent intersubunit electrostatic interactions between E955 in RCK2 and R786 and R790 in the RCK2 of the adjacent subunit...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29319175/bk-channels-blockage-inhibits-hypoxia-induced-migration-and-chemoresistance-to-cisplatin-in-human-glioblastoma-cells
#17
Paolo Rosa, Luigi Catacuzzeno, Luigi Sforna, Giorgio Mangino, Silvia Carlomagno, Gabriella Mincione, Vincenzo Petrozza, Giuseppe Ragona, Fabio Franciolini, Antonella Calogero
Glioblastoma (GBM) cells express large-conductance, calcium-activated potassium (BK) channels, whose activity is important for several critical aspects of the tumor, such as migration/invasion and cell death. GBMs are also characterized by a heavy hypoxic microenvironment that exacerbates tumor aggressiveness. Since hypoxia modulates the activity of BK channels in many tissues, we hypothesized that a hypoxia-induced modulation of these channels may contribute to the hypoxia-induced GBM aggressiveness. In U87-MG cells, hypoxia induced a functional upregulation of BK channel activity, without interfering with their plasma membrane expression...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29290926/trafficking-of-bk-channel-subunits-controls-arterial-contractility
#18
EDITORIAL
M Dennis Leo, Jonathan H Jaggar
No abstract text is available yet for this article.
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29259649/chloroform-extract-of-artemisia-annua-l-relaxes-mouse-airway-smooth-muscle
#19
Jun Huang, Li-Qun Ma, Yongle Yang, Nana Wen, Wan Zhou, Congli Cai, Qing-Hua Liu, Jinhua Shen
Artemisia annua L. belongs to the Asteraceae family, which is indigenous to China. It has valuable pharmacological properties, such as antimalarial, anti-inflammatory, and anticancer properties. However, whether it possesses antiasthma properties is unknown. In the current study, chloroform extract of Artemisia annua L. (CEAA) was prepared, and we found that CEAA completely eliminated acetylcholine (ACh) or high K+-elicited (80 mM) contractions of mouse tracheal rings (TRs). Patch-clamp technique and ion channel blockers were employed to explore the underlying mechanisms of the relaxant effect of CEAA...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29248193/effects-of-mechanical-stretch-on-the-functions-of-bk-and-l-type-ca-2-channels-in-vascular-smooth-muscle-cells
#20
Zhiguo Zhang, Yuqiao Wen, Jing Du, Yang Yu, Sisi Liu, Xiaoan Wu, Hucheng Zhao
It is well recognized that pathologically increased mechanical stretch plays a critical role in vascular remodeling during hypertension. However, how the stretch modulates the functions of ion channels of vascular smooth muscle cells (VSMCs) remains to be elucidated. Here, we demonstrated the effects of mechanical stretch on the activity of large conductance calcium, voltage-activated potassium (BK) and L-type Ca2+channels. In comparison with 5% stretch (physiological), 15% stretch (pathological) upregulated the current density of L-type Ca2+and BK channels as well as the frequency and amplitude of calcium oscillation in VSMCs...
January 23, 2018: Journal of Biomechanics
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