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Maxi k channel

Igor Voznesensky, Kenneth J DeLay, Wayne J G Hellstrom
Cardiovascular disease (CVD) and erectile dysfunction (ED) are two disease processes that affect millions of men. CVD and ED are increasingly recognized as sharing a common pathophysiologic origin. As the nature of this relationship continues to be elucidated, there is growing interest in developing a therapy to effectively target both processes. While researchers have largely focused on phosphodiesterase-5 inhibitors (PDE5Is), the established first-line therapy for ED, newer ED drugs, designed based on better understanding of the physiology of erection, may also show promise...
October 8, 2016: Expert Opinion on Pharmacotherapy
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
H Kim, K H Oh
The large conductance, voltage- and calcium-dependent potassium BK channel, also termed BKCa, Maxi-K, KCa1.1, or SLO1, regulates a wide array of key biological processes that are mediated by calcium ions. This broad regulatory function of BK channels requires the interactions of BK channels with diverse sets of proteins that have different molecular or cellular functions. Proteins that interact with BK channels range from the auxiliary subunits of BK channels to cytoskeletal proteins responsible for BK channel trafficking and localization...
2016: International Review of Neurobiology
Yue Li, Hongxiang Hu, Michael B Butterworth, Jin-Bin Tian, Michael X Zhu, Roger G O'Neil
The voltage- and Ca2+-activated, large conductance K+ channel (BK, maxi-K) is expressed in the collecting duct system of kidney where it underlies flow- and Ca2+-dependent K+ excretion. To determine if other Ca2+-activated K+ channels (KCa) may participate in this process, mouse kidney and the K+-secreting mouse cortical collecting duct (CCD) cell line, mCCDcl1, were assessed for TRPV4 and KCa channel expression and cross-talk. qPCR mRNA analysis and immunocytochemical staining demonstrated TRPV4 and KCa expression in mCCDcl1 cells and kidney connecting tubule (CNT) and CCD...
2016: PloS One
Bernat Elvira, Yogesh Singh, Jamshed Warsi, Carlos Munoz, Florian Lang
BACKGROUND/AIMS: The oxidative stress-responsive kinase 1 (OSR1) and the serine/threonine kinases SPAK (SPS1-related proline/alanine-rich kinase) are under the control of WNK (with-no-K [Lys]) kinases. OSR1 and SPAK participate in diverse functions including cell volume regulation and neuronal excitability. Cell volume and neuronal excitation are further modified by the large conductance Ca2+-activated K+ channels (maxi K+ channel or BK channels). An influence of OSR1 and/or SPAK on BK channel activity has, however, never been shown...
2016: Cellular Physiology and Biochemistry
Alsu N Mustafina, Aleksey V Yakovlev, Aisylu Sh Gaifullina, Thomas M Weiger, Anton Hermann, Guzel F Sitdikova
The aim of the present study was to evaluate the effects of hydrogen sulfide (H2S) on the membrane potential, action potential discharge and exocytosis of secretory granules in neurosecretory pituitary tumor cells (GH3). The H2S donor - sodium hydrosulfide (NaHS) induced membrane hyperpolarization, followed by truncation of spontaneous electrical activity and decrease of the membrane resistance. The NaHS effect was dose-dependent with an EC50 of 152 μM (equals effective H2S of 16-19 μM). NaHS effects were not altered after inhibition of maxi conductance calcium-activated potassium (BK) channels by tetraethylammonium or paxilline, but were significantly reduced after inhibition or activation of ATP-dependent potassium channels (KATP) by glibenclamide or by diazoxide, respectively...
October 2, 2015: Biochemical and Biophysical Research Communications
Sajjad Salari, Maedeh Ghasemi, Javad Fahanik-Babaei, Reza Saghiri, Remy Sauve, Afsaneh Eliassi
We report in a previous study the presence of a large conductance K+ channel in the membrane of rough endoplasmic reticulum (RER) from rat hepatocytes incorporated into lipid bilayers. Channel activity in this case was found to decrease in presence of ATP 100 µM on the cytoplasmic side and was totally inhibited at ATP concentrations greater than 0.25 mM. Although such features would be compatible with the presence of a KATP channel in the RER, recent data obtained from a brain mitochondrial inner membrane preparation have provided evidence for a Maxi-K channel which could also be blocked by ATP within the mM concentration range...
2015: PloS One
Taylor C Peak, Faysal A Yafi, Premsant Sangkum, Wayne J G Hellstrom
INTRODUCTION: Erectile dysfunction adversely affects the lives of millions of men, and is the most commonly treated sexual disorder today. The erectile process has been extensively investigated, with major advances made in elucidating many of the complex molecular pathways involved. These advances have allowed researchers to design and study drug formulations that target various aspects of this complex process. The initial culmination of this research was the introduction of phosphodiesterase 5-inhibitors...
June 2015: Expert Opinion on Emerging Drugs
Andreas Genewsky, Ingmar Jost, Catharina Busch, Christian Huber, Julia Stindl, Christine Skerka, Peter F Zipfel, Bärbel Rohrer, Olaf Strauß
Defective regulation of the alternative pathway of the complement system is believed to contribute to damage of retinal pigment epithelial (RPE) cells in age-related macular degeneration. Thus we investigated the effect of complement activation on the RPE cell membrane by analyzing changes in membrane conductance via patch-clamp techniques and Ca(2+) imaging. Exposure of human ARPE-19 cells to complement-sufficient normal human serum (NHS) (25 %) resulted in a biphasic increase in intracellular free Ca(2+) ([Ca(2+)]i); an initial peak followed by sustained Ca(2+) increase...
October 2015: Pflügers Archiv: European Journal of Physiology
Bin Wang, David B Jaffe, Robert Brenner
While most large-conductance, calcium-, and voltage-activated potassium channels (BK or Maxi-K type) are blocked by the scorpion venom iberiotoxin, the so-called "type II" subtype has the property of toxin resistance. This property is uniquely mediated by channel assembly with one member of the BK accessory β subunit family, the neuron-enriched β4 subunit. This review will focus on current understanding of iberiotoxin-resistant, β4-containing BK channel properties and their function in the CNS. Studies have shown that β4 dramatically promotes BK channel opening by shifting voltage sensor activation to more negative voltage ranges, but also slows activation to timescales that theoretically preclude BK ability to shape action potentials (APs)...
2014: Frontiers in Physiology
Mark R Tanner, Xueyou Hu, Redwan Huq, Rajeev B Tajhya, Liang Sun, Fatima S Khan, Teresina Laragione, Frank T Horrigan, Pércio S Gulko, Christine Beeton
OBJECTIVE: Fibroblast-like synoviocytes (FLS) participate in joint inflammation and damage in rheumatoid arthritis (RA) and its animal models. The purpose of this study was to define the importance of KCa1.1 (BK, Maxi-K, Slo1, KCNMA1) channel expression and function in FLS and to establish these channels as potential new targets for RA therapy. METHODS: We compared KCa1.1 expression levels in FLS from rats with pristane-induced arthritis (PIA) and in FLS from healthy rats...
January 2015: Arthritis & Rheumatology
Oscar Vivas, Martin Kruse, Bertil Hille
Levels of nerve growth factor (NGF) are elevated in inflamed tissues. In sensory neurons, increases in NGF augment neuronal sensitivity (sensitization) to noxious stimuli. Here, we hypothesized that NGF also sensitizes sympathetic neurons to proinflammatory stimuli. We cultured superior cervical ganglion (SCG) neurons from adult male Sprague Dawley rats with or without added NGF and compared their responsiveness to bradykinin, a proinflammatory peptide. The NGF-cultured neurons exhibited significant depolarization, bursts of action potentials, and Ca(2+) elevations after bradykinin application, whereas neurons cultured without NGF showed only slight changes in membrane potential and cytoplasmic Ca(2+) levels...
September 3, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lisheng Ge, Neil T Hoa, Zechariah Wilson, Gabriel Arismendi-Morillo, Xiao-Tang Kong, Rajeev B Tajhya, Christine Beeton, Martin R Jadus
The Big Potassium (BK) ion channel is commonly known by a variety of names (Maxi-K, KCNMA1, slo, stretch-activated potassium channel, KCa1.1). Each name reflects a different physical property displayed by this single ion channel. This transmembrane channel is found on nearly every cell type of the body and has its own distinctive roles for that tissue type. The BKα channel contains the pore that releases potassium ions from intracellular stores. This ion channel is found on the cell membrane, endoplasmic reticulum, Golgi and mitochondria...
October 2014: International Immunopharmacology
Jonathan Berrout, Mykola Mamenko, Oleg L Zaika, Lihe Chen, Wenzheng Zang, Oleh Pochynyuk, Roger G O'Neil
The Ca2+-activated, maxi-K (BK) K+ channel, with low Ca2+-binding affinity, is expressed in the distal tubule of the nephron and contributes to flow-dependent K+ secretion. In the present study we demonstrate that the Ca2+-activated, SK3 (KCa2.3) K+ channel, with high Ca2+-binding affinity, is also expressed in the mouse kidney (RT-PCR, immunoblots). Immunohistochemical evaluations using tubule specific markers demonstrate significant expression of SK3 in the distal tubule and the entire collecting duct system, including the connecting tubule (CNT) and cortical collecting duct (CCD)...
2014: PloS One
Zohreh Hosseinzadeh, Ahmad Almilaji, Sabina Honisch, Tatsiana Pakladok, GuoXing Liu, Shefalee K Bhavsar, Peter Ruth, Ekaterina Shumilina, Florian Lang
The iberiotoxin-sensitive large conductance voltage- and Ca(2+)-activated potassium (BK) channels (maxi-K(+)-channels) hyperpolarize the cell membrane thus supporting Ca(2+) entry through Ca(2+)-release activated Ca(2+) channels. Janus kinase-2 (JAK2) has been identified as novel regulator of ion transport. To explore whether JAK2 participates in the regulation of BK channels, cRNA encoding Ca(2+)-insensitive BK channels (BK(M513I+Δ899-903)) was injected into Xenopus oocytes with or without cRNA encoding wild-type JAK2, gain-of-function (V617F)JAK2, or inactive (K882E)JAK2...
June 1, 2014: American Journal of Physiology. Cell Physiology
Helga Vitzthum, Anika Seniuk, Laura Helene Schulte, Maxie Luise Müller, Hannah Hetz, Heimo Ehmke
A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load...
March 1, 2014: Journal of Physiology
George W J Wright, Sean P Parsons, Raúl Loera-Valencia, Xuan-Yu Wang, Carlos Barajas-López, Jan D Huizinga
Interstitial cells of Cajal (ICC) and the enteric nervous system orchestrate the various rhythmic motor patterns of the colon. Excitation of ICC may evoke stimulus-dependent pacemaker activity and will therefore have a profound effect on colonic motility. The objective of the present study was to evaluate the potential role of K(+) channels in the regulation of ICC excitability. We employed the cell-attached patch clamp technique to assess single channel activity from mouse colon ICC, immunohistochemistry to determine ICC K(+) channel expression and single cell RT-PCR to identify K(+) channel RNA...
September 2014: Pflügers Archiv: European Journal of Physiology
Maria I Georgi, Julia Rosendahl, Franziska Ernst, Dorothee Günzel, Jörg R Aschenbach, Holger Martens, Friederike Stumpff
It has long been established that the absorption of short-chain fatty acids (SCFA) across epithelia stimulates sodium proton exchange. The apically released protons are not available as countercations for the basolateral efflux of SCFA anions and a suitable transport model is lacking. Patch clamp and microelectrode techniques were used to characterize an anion conductance expressed by cultured cells of the sheep and bovine rumen and the sheep omasum and to localize the conductance in the intact tissue. Cells were filled with a Na-gluconate solution and superfused with sodium salts of acetate, propionate, butyrate, or lactate...
September 2014: Pflügers Archiv: European Journal of Physiology
Seung-Kuy Cha, Ji-Hee Kim, Chou-Long Huang
TRPV5 and TRPV6 channels are expressed in distal renal tubules and play important roles in the transcellular Ca(2+) reabsorption in kidney. They are regulated by multiple intracellular factors including protein kinases A and C, membrane phospholipid PIP2, protons, and divalent ions Ca(2+) and Mg(2+). Here, we report that fluid flow that generates shear force within the physiological range of distal tubular fluid flow activated TRPV5 and TRPV6 channels expressed in HEK cells. Flow-induced activation of channel activity was reversible and did not desensitize over 2min...
December 2013: Biochimica et Biophysica Acta
Mustapha Irnaten, Richard C Barry, Deborah M Wallace, Neil G Docherty, Barry Quill, Abbot F Clark, Colm J O'Brien
The connective tissue plates of the lamina cribrosa (LC) region are continuously exposed to a mechanically dynamic environment. To study how the LC cells respond to these mechanical forces, we measured the mechano-sensitive calcium dependent maxi-K(+) ion channel current in the cell membrane of LC cells of glaucoma and normal subjects. Primary culture LC cells from 7 normal and 7 age matched glaucoma donors were studied. Perfusion of cells with hypotonic solution was used to stretch the cell membrane. Whole-cell patch-clamp technique was used to measure the basal (non stretched) and hypotonic stretch-induced changes in maxi-K(+) ion channel activity in normal and glaucoma LC cells...
October 2013: Experimental Eye Research
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