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https://www.readbyqxmd.com/read/27898416/sgk3-sensitivity-of-large-conductance-ca2-activated-k-channel
#1
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
https://www.readbyqxmd.com/read/27872281/interactions-of-divalent-cations-with-calcium-binding-sites-of-bk-channels-reveal-independent-motions-within-the-gating-ring
#2
Pablo Miranda, Teresa Giraldez, Miguel Holmgren
Large-conductance voltage- and calcium-activated K(+) (BK) channels are key physiological players in muscle, nerve, and endocrine function by integrating intracellular Ca(2+) and membrane voltage signals. The open probability of BK channels is regulated by the intracellular concentration of divalent cations sensed by a large structure in the BK channel called the "gating ring," which is formed by four tandems of regulator of conductance for K(+) (RCK1 and RCK2) domains. In contrast to Ca(2+) that binds to both RCK domains, Mg(2+), Cd(2+), or Ba(2+) interact preferentially with either one or the other...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27872049/contribution-of-kv1-5-channel-to-h2o2-induced-human-arteriolar-dilation-and-its-modulation-by-coronary-artery-disease
#3
Yoshinori Nishijima, Sheng Cao, Dawid S Chabowski, Ankush Korishettar, Alyce Ge, Xiaodong Zheng, Rodney Sparapani, David D Gutterman, David X Zhang
RATIONALE: Hydrogen peroxide (H2O2) regulates vascular tone in the human microcirculation under physiological and pathophysiological conditions. It dilates arterioles by activating BKCa channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) as compared to those with CAD remain unknown. OBJECTIVE: We hypothesize that H2O2-elicited dilation involves different K(+) channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation during disease...
November 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27856251/local-calcium-signalling-is-mediated-by-mechanosensitive-ion-channels-in-mesenchymal-stem-cells
#4
Vladislav I Chubinskiy-Nadezhdin, Valeria Y Vasileva, Natalia A Pugovkina, Irina O Vassilieva, Elena A Morachevskaya, Nikolay N Nikolsky, Yuri A Negulyaev
Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs)...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27849612/atomic-determinants-of-bk-channel-activation-by-polyunsaturated-fatty-acids
#5
Yutao Tian, Marius Aursnes, Trond Vidar Hansen, Jørn Eivind Tungen, Jason D Galpin, Lilia Leisle, Christopher A Ahern, Rong Xu, Stefan H Heinemann, Toshinori Hoshi
Docosahexaenoic acid (DHA), a polyunsaturated ω-3 fatty acid enriched in oily fish, contributes to better health by affecting multiple targets. Large-conductance Ca(2+)- and voltage-gated Slo1 BK channels are directly activated by nanomolar levels of DHA. We investigated DHA-channel interaction by manipulating both the fatty acid structure and the channel composition through the site-directed incorporation of unnatural amino acids. Electrophysiological measurements show that the para-group of a Tyr residue near the ion conduction pathway has a critical role...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27834847/astaxanthin-and-docosahexaenoic-acid-reverse-the-toxicity-of-the-maxi-k-bk-channel-antagonist-mycotoxin-penitrem-a
#6
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
https://www.readbyqxmd.com/read/27827370/ethanol-sensitive-pacemaker-neurons-in-the-mouse-external-globus-pallidus
#7
Karina P Abrahao, Jessica H Chancey, C Savio Chan, David M Lovinger
Although ethanol is one of the most widely used drugs, we still lack a full understanding of which neuronal subtypes are affected by this drug. Pacemaker neurons exert powerful control over brain circuit function, but little is known about ethanol effects on these types of neurons. Neurons in the external Globus Pallidus (GPe) generate pacemaker activity that controls basal ganglia, circuitry associated with habitual and compulsive drug use. We performed patch-clamp recordings from GPe neurons. We found that bath application of ethanol dose-dependently decreased the firing rate of low frequency GPe neurons, but did not alter the firing of high frequency neurons...
November 9, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27812391/use-of-aldosterone-antagonist-to-treat-diarrhea-and-hypokalemia-of-ogilvie-s-syndrome
#8
Pradhum Ram, Abhinav Goyal, Marvin Lu, Joshua Sloan, William McElhaugh
Ogilvie's syndrome (OS) is a functional obstruction of the bowel due to an autonomic imbalance. It often presents with diarrhea and is associated with hypokalemia. We present a case of a 70-year-old male who developed severe abdominal distension, watery diarrhea, and persistent hypokalemia status after left hip arthroplasty after suffering from a femoral neck fracture due to a fall and was diagnosed with OS. The persistent hypokalemia was slow to improve despite aggressive repletion because of the high potassium losses in the stool...
2016: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/27807200/molecular-determinants-of-bk-channel-functional-diversity-and-functioning
#9
REVIEW
Ramon Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V Sepulveda, Fernando Gonzalez-Nilo, Carlos Gonzalez, Osvaldo Alvarez
Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca(2+) binding sites) communicate with the pore gates allosterically...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27806944/the-mechanosensitive-bk%C3%AE-%C3%AE-1-channel-localizes-to-cilia-of-principal-cells-in-rabbit-cortical-collecting-duct-ccd
#10
Rolando Carrisoza-Gaytán, Lijun Wang, Carlos M N 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 for 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...
November 2, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27806708/ryanodine-induced-vasoconstriction-of-the-gerbil-spiral-modiolar-artery-depends-on-the-ca-2-sensitivity-but-not-on-ca-2-sparks-or-bk-channels
#11
Gayathri Krishnamoorthy, Katrin Reimann, Philine Wangemann
BACKGROUND: In many vascular smooth muscle cells (SMCs), ryanodine receptor-mediated Ca(2+) sparks activate large-conductance Ca(2+)-activated K(+) (BK) channels leading to lowered SMC [Ca(2+)]i and vasodilation. Here we investigated whether Ca(2+) sparks regulate SMC global [Ca(2+)]i and diameter in the spiral modiolar artery (SMA) by activating BK channels. METHODS: SMAs were isolated from adult female gerbils, loaded with the Ca(2+)-sensitive flourescent dye fluo-4 and pressurized using a concentric double-pipette system...
November 2, 2016: BMC Physiology
https://www.readbyqxmd.com/read/27799321/alcohol-modulation-of-bk-channel-gating-depends-on-%C3%AE-subunit-composition
#12
Guruprasad Kuntamallappanavar, Alex M Dopico
In most mammalian tissues, Ca(2+)i/voltage-gated, large conductance K(+) (BK) channels consist of channel-forming slo1 and auxiliary (β1-β4) subunits. When Ca(2+)i (3-20 µM) reaches the vicinity of BK channels and increases their activity at physiological voltages, β1- and β4-containing BK channels are, respectively, inhibited and potentiated by intoxicating levels of ethanol (50 mM). Previous studies using different slo1s, lipid environments, and Ca(2+)i concentrations-all determinants of the BK response to ethanol-made it impossible to determine the specific contribution of β subunits to ethanol action on BK activity...
November 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27798183/%C3%AE-2%C3%AE-2-controls-the-function-and-trans-synaptic-coupling-of-cav1-3-channels-in-mouse-inner-hair-cells-and-is-essential-for-normal-hearing
#13
Barbara Fell, Stephanie Eckrich, Kerstin Blum, Tobias Eckrich, Dietmar Hecker, Gerald J Obermair, Stefan Münkner, Veit Flockerzi, Bernhard Schick, Jutta Engel
: The auxiliary subunit α2δ2 modulates the abundance and function of voltage-gated calcium channels. Here we show that α2δ2 mRNA is expressed in neonatal and mature hair cells. A functional α2δ2-null mouse, the ducky mouse (du), showed elevated auditory brainstem response click and frequency-dependent hearing thresholds. Otoacoustic emissions were not impaired pointing to normal outer hair cell function. Peak Ca(2+) and Ba(2+) currents of mature du/du inner hair cells (IHCs) were reduced by 30-40%, respectively, and gating properties, such as the voltage of half-maximum activation and voltage sensitivity, were altered, indicating that Cav1...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27789734/elevated-k-channel-activity-opposes-vasoconstrictor-response-to-serotonin-5-ht-in-cerebral-arteries-of-the-fawn-hooded-hypertensive-rat
#14
Mallikarjuna R Pabbidi, Richard J Roman
Previous studies suggest that middle cerebral arteries (MCAs) of Fawn Hooded Hypertensive (FHH) rats exhibit impaired myogenic response and introgression of small region of Brown Norway chromosome 1 containing 15 genes restored the response in FHH.1(BN) congenic rat. The impaired myogenic response in FHH rats is associated with an increase in the activity of the large conductance potassium (BK) channel in vascular smooth muscle cells (VSMCs). The present study examined whether the increased BK channel function in FHH rat alters vasoconstrictor response to serotonin (5-HT)...
October 27, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27765747/hydrogen-sulfide-induced-vasodilation-mediated-by-endothelial-trpv4-channels
#15
Jay S Naik, Jessica M Osmond, Benjimen R Walker, Nancy L Kanagy
Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large-conductance Ca(2+)-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium...
December 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27763639/functional-kca1-1-channels-are-crucial-for-regulating-the-proliferation-migration-and-differentiation-of-human-primary-skeletal-myoblasts
#16
Rajeev B Tajhya, Xueyou Hu, Mark R Tanner, Redwan Huq, Natee Kongchan, Joel R Neilson, George G Rodney, Frank T Horrigan, Lubov T Timchenko, Christine Beeton
Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1...
October 20, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27758860/a-new-splice-variant-of-large-conductance-ca2-activated-k-bk-channel-%C3%AE-subunit-alters-human-chondrocyte-function
#17
Yoshiaki Suzuki, Susumu Ohya, Hisao Yamamura, Wayne R Giles, Yuji Imaizumi
Large conductance Ca(2+)-activated K(+) (BK) channels play essential roles in both excitable and non-excitable cells. For example, in chondrocytes, agonist-induced Ca(2+) release from intracellular store activates BK channels, and this hyperpolarizes these cells, augments Ca(2+) entry, and forms a positive feed-back mechanism for Ca(2+) signaling and stimulation-secretion coupling. In the present study, functional roles of a newly identified splice variant in the BK channel α subunit (BKαΔe2) were examined in a human chondrocyte cell line, OUMS-27, and in a HEK293 expression system...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27755549/single-channel-recordings-reveal-differential-%C3%AE-2-subunit-modulations-between-mammalian-and-drosophila-bkca-%C3%AE-2-channels
#18
Zhenzhen Yan, Bin Hu, Zhigang Huang, Ling Zhong, Xiying Guo, Anxi Weng, Feng Xiao, Wenping Zeng, Yan Zhang, Jiuping Ding, Panpan Hou
Large-conductance Ca2+- and voltage-activated potassium (BK) channels are widely expressed in tissues. As a voltage and calcium sensor, BK channels play significant roles in regulating the action potential frequency, neurotransmitter release, and smooth muscle contraction. After associating with the auxiliary β2 subunit, mammalian BK(β2) channels (mouse or human Slo1/β2) exhibit enhanced activation and complete inactivation. However, how the β2 subunit modulates the Drosophila Slo1 channel remains elusive...
2016: PloS One
https://www.readbyqxmd.com/read/27747371/estradiol-modified-prolactin-secretion-independently-of-action-potentials-and-ca-2-and-blockade-of-outward-potassium-currents-in-gh3-cells
#19
Manuel Sánchez, Lorena Suárez, Begoña Cantabrana, Javier Bordallo
Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca(2+) associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca(2+) and noninactivating K(+) currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH3...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27733613/alcohol-regulates-bk-surface-expression-via-wnt-%C3%AE-catenin-signaling
#20
Cristina Velázquez-Marrero, Alexandra Burgos, José O García, Stephanie Palacio, Héctor G Marrero, Alexandra Bernardo, Juliana Pérez-Laspiur, Marla Rivera-Oliver, Garrett Seale, Steven N Treistman
: It has been suggested that drug tolerance represents a form of learning and memory, but this has not been experimentally established at the molecular level. We show that a component of alcohol molecular tolerance (channel internalization) from rat hippocampal neurons requires protein synthesis, in common with other forms of learning and memory. We identify β-catenin as a primary necessary protein. Alcohol increases β-catenin, and blocking accumulation of β-catenin blocks alcohol-induced internalization in these neurons...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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