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Maxi k channel

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
Friederike Stumpff
Fermentative organs such as the caecum, the colon, and the rumen have evolved to produce and absorb energy rich short chain fatty acids (SCFA) from otherwise indigestible substrates. Classical models postulate diffusional uptake of the undissociated acid (HSCFA). However, in net terms, a major part of SCFA absorption occurs with uptake of Na+ and resembles classical, coupled electroneutral NaCl transport. Considerable evidence suggests that the anion transporting proteins expressed by epithelia of fermentative organs are poorly selective and that their main function may be to transport acetate-, propionate-, butyrate- and HCO3- as the physiologically relevant anions...
January 6, 2018: Pflügers Archiv: European Journal of Physiology
Vipin Sharma, Sooraj V Nair, Pooja Jaitley, Udayraj P Nakade, Abhishek Sharma, Soumen Choudhury, Satish Kumar Garg
Cellular coupling of beta3 -adrenoceptors (β3 -ADR) to potassium channels in myometrium is largely unknown. In vitro study was undertaken to unravel the presence of β3 -adrenergic receptors (ADR) and the role of K+ -channels in mediating β3 -ADR-induced relaxation in isolated myometrial strips from cyclic non-pregnant water buffaloes. Isometric tension was recorded in isolated myometrial strips using data acquisition system based physiograph. Compared to SR 59230A, BRL 37344 was found to be more potent in inducing β3 -dependent myometrial relaxation which was significantly (p < 0...
February 2018: Theriogenology
Eun Yeong Suh, Ming Zhe Yin, Haiyue Lin, Yin Hua Zhang, Hae Young Yoo, Sung Joon Kim
Arterioles and small arteries change their tone in response to transmural pressure changes, called myogenic tone (MT). In comparison to the branches of cerebral arteries (CA) showing prominent MT, the third branches of mesenteric arteries (MA) with similar diameters show weaker MT Here, we aimed to analyze the electrophysiological differences responsible for the weaker MT in MA (MTMA) than MT in CA (MTCA). We measured ionic current using patch clamp in isolated MA smooth muscle cells (MASMCs) and CA smooth muscle cells (CASMCs) of rats...
July 2017: Physiological Reports
Ji-Kan Ryu, Jun-Kyu Suh, Arthur L Burnett
Although oral phosphodiesterase-5 (PDE5) inhibitors are generally accepted as an effective therapy for erectile dysfunction (ED), men with ED from diabetes or radical prostatectomy respond poorly to these drugs. Many researchers have tried to develop novel therapeutics that target alternative molecular pathways. A group of therapeutics belongs to centrally acting agents that target dopamine and melanocortin receptors. The other one is the peripherally acting agents that target soluble guanylate cyclase, Rho-kinase pathway, and Maxi-K channel, etc...
April 2017: Translational Andrology and Urology
Mykola V Mamenko, Nabila Boukelmoune, Viktor N Tomilin, Oleg L Zaika, V Behrana Jensen, Roger G O'Neil, Oleh M Pochynyuk
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells...
June 2017: Kidney International
Khaled Boobés, Robert M Rosa, Daniel Batlle
Ogilvie's syndrome, or acute colonic pseudo-obstruction, is characterized by massive dilation of the colon without mechanical obstruction. Water and electrolytes often can be sequestered in the dilated intestinal loops resulting in profuse and watery diarrhea as well as hypokalemia. We report an anuric, end-stage renal disease (ESRD) patient undergoing peritoneal dialysis (PD) who developed acute colonic pseudo-obstruction causing a prolonged hospitalization. He also developed severe hypokalemia with a serum potassium (K+) as low as 2...
March 2017: Clinical Nephrology
Musaab Ahmed, Myriam Fezai, Florian Lang
BACKGROUND/AIMS: Large conductance Ca2+-activated K+ channels (maxi K+ channels or BK channels) are rapidly activated by increase of cytosolic Ca2+ activity. The channels participate in the regulation of diverse functions including neuronal excitation and cell volume. The BK channels may be modified by kinases. Channel regulating kinases include the serum & glucocorticoid inducible kinase 3 (SGK3). The present study explored whether SGK3 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 SGK3, constitutively active S419DSGK3, or catalytically inactive K191NSGK3...
November 30, 2016: Neuro-Signals
Amira A Goda, Khayria M Naguib, Magdy M Mohamed, Hassan A Amra, Somaia A Nada, Abdel-Rahman B Abdel-Ghaffar, Chris R Gissendanner, Khalid A El Sayed
Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects...
November 9, 2016: Marine Drugs
Rolando Carrisoza-Gaytán, Lijun Wang, Carlos Schreck, Thomas R Kleyman, Wen-Hui Wang, Lisa M Satlin
Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca(2+)- and/or stretch-dependent flow-induced K(+) secretion (FIKS) and contributes to K(+) adaptation in response to dietary K(+) loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K(+) secretory processes. In support of a role for ICs in FIKS is the higher density of immunoreactive apical BKα (pore-forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα expression in response to a high-K(+) diet...
January 1, 2017: American Journal of Physiology. Renal Physiology
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...
December 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
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