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https://www.readbyqxmd.com/read/28487419/membrane-depolarization-activates-bk-channels-through-rock-mediated-%C3%AE-1-subunit-surface-trafficking-to-limit-vasoconstriction
#1
M Dennis Leo, Xue Zhai, Padmapriya Muralidharan, Korah P Kuruvilla, Simon Bulley, Frederick A Boop, Jonathan H Jaggar
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca(2+))-activated potassium (BK) channels, which limits Ca(2+) channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28487418/science-signaling-podcast-for-9-may-2017-trafficking-of-bk-channel-subunits-in-arterial-myocytes
#2
Jonathan H Jaggar, Annalisa M VanHook
This Podcast features a conversation with Jonathan Jaggar, senior author of a Research Article that appears in the 9 May 2017 issue of Science Signaling, about trafficking of big potassium (BK) channel subunits in arterial myocytes. Depolarization of the arterial myocyte membrane causes a rise in intracellular calcium that stimulates the cell to contract, which leads to vasoconstriction. Membrane depolarization also activates BK channels, which allow potassium to flow out of the cell, thus repolarizing the membrane and promoting vasodilation...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28481415/large-conductance-ca-2-activated-k-channel-activation-by-apical-p2y-receptor-agonists-requires-hydrocortisone-in-differentiated-airway-epithelium
#3
Nathan A Zaidman, Angela Panoskaltsis-Mortari, Scott M O'Grady
In the present study we investigated the role of hydrocortisone (HC) on UTP-stimulated ion transport in differentiated, pseudostratified epithelia derived from normal human bronchial basal cells. The presence of a UTP stimulated, paxilline-sensitive large conductance Ca(2+) -activated K(+) (BK) current was demonstrated in control epithelia but was not stimulated in epithelia differentiated in the absence of HC (HC0). Addition of the BK opener NS11021 directly activated channels in control epithelia however under HC0 conditions, activation only occurred when UTP was added after NS11021...
May 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28469792/large-conductance-voltage-and-ca-2-activated-k-channels-affect-the-physiological-characteristics-of-human-urine-derived-stem-cells
#4
Qingqing Wang, Jiang Zhao, Chao Wu, Zhenxing Yang, Xingyou Dong, Qian Liu, Bishao Sun, Chen Wei, Xiaoyan Hu, Longkun Li
We investigated the current characteristics of large conductance voltage and Ca(2+)-activated K(+) (BK) channels in human urine-derived stem cells (hUSCs) and the effect of BK channels on proliferation and differentiation of hUSCs. Fresh human urine (n=6) was collected from healthy donors to isolate hUSCs. Human KCNMA1 gene silencing U6 shRNA was used to down regulate the expression of BK in hUSCs. IBTX (BK channel antagonist) and NS1619 (BK channel agonist) were used to examine the effect of BK channels on hUSCs...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28468834/a-voltage-dependent-k-channel-in-the-lysosome-is-required-for-refilling-lysosomal-ca-2-stores
#5
Wuyang Wang, Xiaoli Zhang, Qiong Gao, Maria Lawas, Lu Yu, Xiping Cheng, Mingxue Gu, Nirakar Sahoo, Xinran Li, Ping Li, Stephen Ireland, Andrea Meredith, Haoxing Xu
The resting membrane potential (Δψ) of the cell is negative on the cytosolic side and determined primarily by the plasma membrane's selective permeability to K(+) We show that lysosomal Δψ is set by lysosomal membrane permeabilities to Na(+) and H(+), but not K(+), and is positive on the cytosolic side. An increase in juxta-lysosomal Ca(2+) rapidly reversed lysosomal Δψ by activating a large voltage-dependent and K(+)-selective conductance (LysoKVCa). LysoKVCa is encoded molecularly by SLO1 proteins known for forming plasma membrane BK channels...
May 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28465407/role-of-nrf2-signaling-in-the-regulation-of-vascular-bk-channel-beta-1-subunit-expression-and-bk-channel-function-in-high-fat-diet-induced-diabetic-mice
#6
Tong Lu, Xiaojing Sun, Yong Li, Qiang Chai, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca(2+)-activated K(+) (BK) channel β1 subunit (BK-β1) is a key modulator of BK channel electrophysiology and the downregulation of BK-β1 protein expression in vascular smooth muscle cells (SMCs) underlies diabetic vascular dysfunction. In this study, we hypothesized that the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway plays a significant role in the regulation of coronary BK channel function and vasodilation in high fat diet (HFD)-induced obese/diabetic mice...
May 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28455309/big-calcium-activated-potassium-channel-in-skeletal-muscle-structure-function-and-pharmacological-perspectives
#7
Fatima Maqoud, Michela Cetrone, Antonietta Mele, Domenico Tricarico
The large-conductance Ca(2+)-activated K(+) (BK) channel is broadly expressed in various mammalian cells and tissues such as neurons, skeletal muscles (sarco-BK), and smooth muscles. These channels are activated by changes in membrane electrical potential and by increases in the concentration of intracellular calcium ion (Ca(2+)). The large-conductance Ca(2+)-activated K(+) (BK) channel is subjected to many mechanisms that add diversity to the BK channel α subunit gene. These channels are indeed subject to alternative splicing, auxiliary subunits modulation, post-translational modifications and protein-protein interactions...
April 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#8
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
#9
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
#10
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-channels-in-retinal-horizontal-cells
#11
Wallace B Thoreson
No abstract text is available yet for this article.
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
#12
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...
May 2, 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
#13
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...
May 1, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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