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https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#1
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28428266/kca1-1-channels-regulate-%C3%AE-1-integrin-function-and-cell-adhesion-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#2
Mark R Tanner, Michael W Pennington, Teresina Laragione, Pércio S Gulko, Christine Beeton
Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of fibroblast-like synoviocytes isolated from the synovium of patients with rheumatoid arthritis (RA-FLS). It is a critical regulator of RA-FLS migration and invasion and therefore represents an attractive target for the therapy of RA. However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness have remained largely unknown. Here, we demonstrate that KCa1...
April 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28424624/commentary-a-bk-slo1-channel-journey-from-molecule-to-physiology
#3
COMMENT
Domenico Tricarico, Antonietta Mele
No abstract text is available yet for this article.
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28418100/a-surprisingly-big-role-for-big-k-bk-channels-in-retinal-horizontal-cells
#4
Wallace B Thoreson
Horizontal cells are lateral inhibitory neurons in the outer part of the retina that receive excitatory synaptic inputs from rod and cone photoreceptors and, in turn, make reciprocal inhibitory contacts back onto photoreceptor synapses This article is protected by copyright. All rights reserved.
April 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28416688/knockout-of-the-lrrc26-subunit-reveals-a-primary-role-of-lrrc26-containing-bk-channels-in-secretory-epithelial-cells
#5
Chengtao Yang, Vivian Gonzalez-Perez, Taro Mukaibo, James E Melvin, Xiao-Ming Xia, Christopher J Lingle
Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca(2+)- and voltage-dependent BK-type K(+) channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca(2+), suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KO mice with a β-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28416647/identifiability-reducibility-and-adaptability-in-allosteric-macromolecules
#6
Gergő Bohner, Gaurav Venkataraman
The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed "allostery," is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca(2+)-activated K(+) (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay...
April 17, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28402883/a-role-of-bk-channel-in-regulation-of-ca-2-channel-in-ventricular-myocytes-by-substrate-stiffness
#7
Hucheng Zhao, Yang Yu, Xiaoan Wu, Sisi Liu, Bailin Liu, Jing Du, Bo Li, Linhua Jiang, Xiqiao Feng
Substrate stiffness is crucial for diverse cell functions, but the mechanisms conferring cells with mechanosensitivity are still elusive. By tailoring substrate stiffness with 10-fold difference, we showed that L-type voltage-gated Ca(2+) channel current density was greater in chick ventricular myocytes cultured on the stiff substrate than on the soft substrate. Blockage of the BK channel increased the Ca(2+) current density on the soft substrate and consequently eliminated substrate stiffness regulation of the Ca(2+) channel...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28373690/a-paternal-methyl-donor-rich-diet-altered-cognitive-and-neural-functions-in-offspring-mice
#8
D P Ryan, K S Henzel, B L Pearson, M E Siwek, A Papazoglou, L Guo, K Paesler, M Yu, R Müller, K Xie, S Schröder, L Becker, L Garrett, S M Hölter, F Neff, I Rácz, B Rathkolb, J Rozman, G Ehninger, M Klingenspor, T Klopstock, E Wolf, W Wurst, A Zimmer, H Fuchs, V Gailus-Durner, M Hrabě de Angelis, K Sidiropoulou, M Weiergräber, Y Zhou, D Ehninger
Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373283/distinct-domains-of-the-%C3%AE-1-subunit-cytosolic-n-terminus-control-surface-expression-and-functional-properties-of-large-conductance-calcium-activated-potassium-bk-channels
#9
Lie Chen, Danlei Bi, Zen Huat Lu, Heather McClafferty, Michael J Shipston
The properties and function of large conductance calcium- and voltage- activated potassium (BK) channels are modified by the tissue specific expression of regulatory β 1-subunits. Although the short cytosolic N-terminal domain of the β 1-subunit is important for controlling both BK channel trafficking and function, whether the same, or different, regions of the N-terminus control these distinct processes remain unknown. Here we demonstrate that the first six N-terminal residues, including K3, K4 and L5, are critical for controlling functional regulation, but not trafficking, of BK channels...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28348135/bk-channels-mediate-synaptic-plasticity-underlying-habituation-in-rats
#10
Tariq Zaman, Cleusa De Oliveira, Mahabba Smoka, Chakravarthi Narla, Michael O Poulter, Susanne Schmid
Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might pay a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices...
March 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28316260/animal-physiology-and-genetic-aspects-of-ryegrass-staggers-in-grazing-sheep
#11
C A Morris, T T Wheeler, H V Henderson, N R Towers, S H Phua
Ryegrass staggers (RGS) is a metabolic disease of herbivores, caused by the ingestion of perennial ryegrass (Lolium perenne L.) containing a fungal endophyte (Neotyphodium lolii) which produces a tremorgenic toxin, lolitrem B. RGS has a major economic impact for agriculture in New Zealand as well as internationally. Management of RGS in grazing sheep can be problematic, and there is an incomplete knowledge of the interaction between the toxin and the grazing animal. This review is focused on recent advances in understanding the molecular physiology of RGS in the affected animal as well as the influence of animal genetics on the degree of susceptibility to RGS...
March 19, 2017: New Zealand Veterinary Journal
https://www.readbyqxmd.com/read/28294531/tyrphostin-ag556-increases-the-activity-of-large-conductance-ca-2-activated-k-channels-by-inhibiting-epidermal-growth-factor-receptor-tyrosine-kinase
#12
Yan Wang, Hai-Ying Sun, Ying-Guang Liu, Zheng Song, Gang She, Guo-Sheng Xiao, Yan Wang, Gui-Rong Li, Xiu-Ling Deng
The present study was designed to investigate whether large conductance Ca(2+) -activated K(+) (BK) channels were regulated by epidermal growth factor (EGF) receptor (EGFR) tyrosine kinase. BK current and channel tyrosine phosphorylation level were measured in BK-HEK 293 cells expressing both functional α-subunits and the auxiliary β1-subunits using electrophysiology, immunoprecipitation and Western blotting approaches, respectively, and the function of rat cerebral basilar arteries was determined with a wire myography system...
March 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28294142/inosine-attenuates-spontaneous-activity-in-the-rat-neurogenic-bladder-through-an-a2b-pathway
#13
Claire Doyle, Vivian Cristofaro, Bryan S Sack, Stefan N Lukianov, Mattias Schäfer, Yeun Goo Chung, Maryrose P Sullivan, Rosalyn M Adam
Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289383/the-citrus-flavanone-naringenin-produces-cardioprotective-effects-in-hearts-from-1-year-old-rat-through-activation-of-mitobk-channels
#14
Lara Testai, Eleonora Da Pozzo, Ilaria Piano, Luisa Pistelli, Claudia Gargini, Maria Cristina Breschi, Alessandra Braca, Claudia Martini, Alma Martelli, Vincenzo Calderone
Background and Purpose: Incidence of cardiovascular disorders increases with age, because of a dramatic fall of endogenous self-defense mechanisms and increased vulnerability of myocardium. Conversely, the effectiveness of many cardioprotective drugs is blunted in hearts of 1 year old rat. The Citrus flavanone naringenin (NAR) was reported to promote cardioprotective effects against ischemia/reperfusion (I/R) injury, through the activation of mitochondrial large conductance calcium-activated potassium channel (mitoBK)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28289184/renal-tubular-ubiquitin-protein-ligase-nedd4-2-is-required-for-renal-adaptation-during-long-term-potassium-depletion
#15
Lama Al-Qusairi, Denis Basquin, Ankita Roy, Renuga Devi Rajaram, Marc P Maillard, Arohan R Subramanya, Olivier Staub
Adaptation of the organism to potassium (K(+)) deficiency requires precise coordination among organs involved in K(+) homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K(+) retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na(+)/Cl(-) cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K(+) restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4L(Pax8/LC1) ) mice exhibited severe hypokalemia and urinary K(+) wasting...
March 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28283888/kinin-receptors-sensitize-trpv4-channel-and-induce-mechanical-hyperalgesia-relevance-to-paclitaxel-induced-peripheral-neuropathy-in-mice
#16
Robson Costa, Maíra A Bicca, Marianne N Manjavachi, Gabriela C Segat, Fabiana Chaves Dias, Elizabeth S Fernandes, João B Calixto
Kinin B1 (B1R) and B2 receptors (B2R) and the transient receptor potential vanilloid 4 (TRPV4) channel are known to play a critical role in the peripheral neuropathy induced by paclitaxel (PTX) in rodents. However, the downstream pathways activated by kinin receptors as well as the sensitizers of the TRPV4 channel involved in this process remain unknown. Herein, we investigated whether kinins sensitize TRPV4 channels in order to maintain PTX-induced peripheral neuropathy in mice. The mechanical hyperalgesia induced by bradykinin (BK, a B2R agonist) or des-Arg(9)-BK (DABK, a B1R agonist) was inhibited by the selective TRPV4 antagonist HC-067047...
March 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28274924/dynamic-coupling-between-trpv4-and-ca-activated-sk1-3-and-ik1-k-channels-plays-a-critical-role-in-regulating-the-k-secretory-bk-channel-in-collecting-duct-cells
#17
Yue Li, Hongxiang Hu, Jin-Bin Tian, Michael X Zhu, Roger G O'Neil
The large conductance Ca2+-activated K+ channel, BK (KCNMA1), is expressed along the connecting tubule (CNT) and cortical collecting duct (CCD) where it underlies flow- and Ca2+-dependent K+ secretion. Its activity is partially under the control of the mechanosensitive TRPV4 Ca2+-permeable channel. Recently we identified three small/intermediate conductance Ca2+-activated K+ channels, SK1 (KCNN1) and SK3 (KCNN3), and IK1 (KCNN4), with notably high Ca2+-binding affinities, that are expressed in CNT/CCD and may be regulated by TRPV4-mediated Ca2+ influx...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28264196/molecular-basis-of-ancestral-vertebrate-electroreception
#18
Nicholas W Bellono, Duncan B Leitch, David Julius
Elasmobranch fishes, including sharks, rays, and skates, use specialized electrosensory organs called ampullae of Lorenzini to detect extremely small changes in environmental electric fields. Electrosensory cells within these ampullae can discriminate and respond to minute changes in environmental voltage gradients through an unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and the big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate (Leucoraja erinacea) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important for the detection of specific, weak electrical signals...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28246116/understanding-the-conformational-motions-of-rck-gating-rings
#19
REVIEW
Teresa Giraldez, Brad S Rothberg
Regulator of conduction of K(+) (RCK) domains are ubiquitous regulators of channel and transporter activity in prokaryotes and eukaryotes. In humans, RCK domains form an integral component of large-conductance calcium-activated K channels (BK channels), key modulators of nerve, muscle, and endocrine cell function. In this review, we explore how the study of RCK domains in bacterial and human channels has contributed to our understanding of the structural basis of channel function. This knowledge will be critical in identifying mechanisms that underlie BK channelopathies that lead to epilepsy and other diseases, as well as regions of the channel that might be successfully targeted to treat such diseases...
April 3, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28242822/survival-and-growth-of-c57bl-6j-mice-lacking-the-bk-channel-kcnma1-lower-adult-body-weight-occurs-together-with-higher-body-fat
#20
Susan T Halm, Michael A Bottomley, Mohammed M Almutairi, Maurico Di Fulvio, Dan R Halm
Big conductance potassium (BK) channels contribute to K(+) flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BK(KO)) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0-P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20-month period of building construction compared with the quiescent period after cessation of construction...
February 2017: Physiological Reports
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