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https://www.readbyqxmd.com/read/29025867/threading-the-biophysics-of-mammalian-slo1-channels-onto-structures-of-an-invertebrate-slo1-channel
#1
REVIEW
Yu Zhou, Huanghe Yang, Jianmin Cui, Christopher J Lingle
For those interested in the machinery of ion channel gating, the Ca(2+) and voltage-activated BK K(+) channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca(2+) and because its large-single channel conductance facilitates detailed kinetic analysis. Over the years, biophysical analyses have illuminated details of the allosteric regulation of BK channels and revealed insights into the mechanism of BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore coupling...
October 12, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29016852/potassium-channel-dysfunction-underlies-purkinje-neuron-spiking-abnormalities-in-spinocerebellar-ataxia-type-2
#2
James M Dell'Orco, Stefan M Pulst, Vikram G Shakkottai
Alterations in Purkinje neuron firing often accompany ataxia, but the molecular basis for these changes is poorly understood. In a mouse model of spinocerebellar ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing frequency accompanies cell atrophy. We investigated the basis for altered Purkinje neuron firing in SCA2. A reduction in the expression of large-conductance calcium-activated potassium (BK) channels and Kv3.3 voltage-gated potassium channels accompanies the inability of Purkinje neurons early in disease to maintain repetitive spiking...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28986465/dendritic-and-axonal-l-type-calcium-channels-cooperate-to-enhance-motoneuron-firing-output-during-drosophila-larval-locomotion
#3
Dimitrios Kadas, Aylin Klein, Niklas Krick, Jason W Worrell, Stefanie Ryglewski, Carsten Duch
Behaviorally adequate neuronal firing patterns are critically dependent on the specific types of ion channel expressed and on their subcellular localization. This study combines in situ electrophysiology with genetic and pharmacological intervention in larval Drosophila melanogaster of both sexes to address localization and function of L-type like calcium channels in motoneurons. We demonstrate that Dmca1D (Cav1 homolog) L-type like calcium channels localize to both, the somatodendritic and the axonal compartment of larval crawling motoneurons...
October 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28979317/the-role-of-bk-channels-in-antiseizure-action-of-the-cb1-receptor-agonist-acea-in-maximal-electroshock-and-pentylenetetrazole-models-of-seizure-in-mice
#4
Sina Asaadi, Mohammad Jahanbakhshi, Mahmoud Lotfinia, Nima Naderi
The anticonvulsant effect of cannabinoid compound has been shown in various models of seizure. On the other hand, there are controversial findings about the role of large conductance calcium-activated potassium (BK) channels in the pathogenesis of epilepsy. Also, there is no data regarding the effect of co-administration of cannabinoid type 1 (CB1) receptor agonists and BK channels antagonists in the acute models of seizure in mice. In this study, the effect of arachidonyl-2'-chloroethylamide (ACEA), a CB1 receptor agonist, and a BK channel antagonist, paxilline, either alone or in combination was investigated...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28966112/functional-validation-of-ca-2-binding-residues-from-the-crystal-structure-of-the-bk-ion-channel
#5
Aravind S Kshatri, Alberto J Gonzalez-Hernandez, Teresa Giraldez
BK channels are dually regulated by voltage and Ca(2+), providing a cellular mechanism to couple electrical and chemical signalling. Intracellular Ca(2+) concentration is sensed by a large cytoplasmic region in the channel known as "gating ring", which is formed by four tandems of regulator of conductance for K(+) (RCK1 and RCK2) domains. The recent crystal structure of the full-length BK channel from Aplysia californica has provided new information about the residues involved in Ca(2+) coordination at the high-affinity binding sites located in the RCK1 and RCK2 domains, as well as their cooperativity...
September 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28955251/molecular-mechanisms-underlying-renin-angiotensin-aldosterone-system-mediated-regulation-of-bk-channels
#6
REVIEW
Zhen-Ye Zhang, Ling-Ling Qian, Ru-Xing Wang
Large-conductance calcium-activated potassium channels (BK channels) belong to a family of Ca(2+)-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone system has profound influences on the expression and bioactivity of BK channels...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28953901/allosteric-activation-mechanism-of-bk-channel-gating-ring-triggered-by-calcium-ions
#7
Ronghua Guan, Hui Zhou, Junwei Li, Shaoying Xiao, Chunli Pang, Yafei Chen, Xiangrong Du, Shaoxi Ke, Qiongyao Tang, Jiguo Su, Yong Zhan, Hailong An
Calcium ions bind at the gating ring which triggers the gating of BK channels. However, the allosteric mechanism by which Ca2+ regulates the gating of BK channels remains obscure. Here, we applied Molecular Dynamics (MD) and Targeted MD to the integrated gating ring of BK channels, and achieved the transition from the closed state to a half-open state. Our date show that the distances of the diagonal subunits increase from 41.0 Å at closed state to 45.7Å or 46.4 Å at a half-open state. It is the rotatory motion and flower-opening like motion of the gating rings which are thought to pull the bundle crossing gate to open ultimately...
2017: PloS One
https://www.readbyqxmd.com/read/28951324/modulation-of-cardiac-vagal-tone-by-bradykinin-acting-on-nucleus-ambiguus
#8
Eugen Brailoiu, Matthew McGuire, Shadaria A Shuler, Elena Deliu, Jeffrey L Barr, Mary E Abood, G Cristina Brailoiu
Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca(2+) concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK...
September 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28940182/bk-%C3%AE-1-subunit-dependent-facilitation-of-ethanol-inhibition-of-bk-current-and-cerebral-artery-constriction-is-mediated-by-the-%C3%AE-1-transmembrane-domain-2
#9
Guruprasad Kuntamallappanavar, Alex M Dopico
BACKGROUND AND PURPOSE: Ethanol at concentrations obtained in circulation during moderate-heavy episodic drinking (30-60 mM) causes cerebral artery constriction in several species, including humans. In rodents, ethanol-induced cerebral artery constriction results from ethanol inhibition of large conductance voltage/Ca(2+)i -gated potassium (BK) channels in cerebral artery myocytes. Moreover, the smooth muscle-abundant BK β1 accessory subunit is required for ethanol to inhibit cerebral artery myocyte BK channels under physiological Ca(2+)i and voltages, and thus constrict cerebral arteries...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28928655/effects-of-simvastatin-beyond-dyslipidemia-exploring-its-antinociceptive-action-in-an-animal-model-of-complex-regional-pain-syndrome-type-i
#10
Graziela Vieira, Juliana Cavalli, Elaine C D Gonçalves, Tainara R Gonçalves, Larissa R Laurindo, Maíra Cola, Rafael C Dutra
Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28928237/microtubule-structures-underlying-the-sarcoplasmic-reticulum-support-peripheral-coupling-sites-to-regulate-smooth-muscle-contractility
#11
Harry A T Pritchard, Albert L Gonzales, Paulo W Pires, Bernard T Drumm, Eun A Ko, Kenton M Sanders, Grant W Hennig, Scott Earley
Junctional membrane complexes facilitate excitation-contraction coupling in skeletal and cardiac muscle cells by forming subcellular invaginations that maintain close (≤20 nm) proximity of ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR) with voltage-dependent Ca(2+) channels in the plasma membrane. In fully differentiated smooth muscle cells, junctional membrane complexes occur as distributed sites of peripheral coupling. We investigated the role of the cytoskeleton in maintaining peripheral coupling and associated Ca(2+) signaling networks within native smooth muscle cells of mouse and rat cerebral arteries...
September 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/28874823/role-of-smad3-and-p38-signalling-in-cigarette-smoke-induced-cftr-and-bk-dysfunction-in-primary-human-bronchial-airway-epithelial-cells
#12
Juliette Sailland, Astrid Grosche, Nathalie Baumlin, John S Dennis, Andreas Schmid, Stefanie Krick, Matthias Salathe
Mucociliary clearance (MCC) is a major airway host defence system that is impaired in patients with smoking-associated chronic bronchitis. This dysfunction is partially related to a decrease of airway surface liquid (ASL) volume that is in part regulated by apically expressed cystic fibrosis transmembrane conductance regulator (CFTR) and large-conductance, Ca(2+)-activated, and voltage dependent K(+) (BK) channels. Here, data from human bronchial epithelial cells (HBEC) confirm that cigarette smoke not only downregulates CFTR activity but also inhibits BK channel function, thereby causing ASL depletion...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865873/statin-therapy-exacerbates-alcohol-induced-constriction-of-cerebral-arteries-via-modulation-of-ethanol-induced-bk-channel-inhibition-in-vascular-smooth-muscle
#13
Maria N Simakova, Shivantika Bisen, Alex M Dopico, Anna N Bukiya
Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo...
September 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28863822/regulation-of-ca-2-sensitive-k-channels-by-cholesterol-and-bile-acids-via-distinct-channel-subunits-and-sites
#14
Alex M Dopico, Anna N Bukiya
Cholesterol (CLR) conversion into bile acids (BAs) in the liver constitutes the major pathway for CLR elimination from the body. Moreover, these steroids regulate each other's metabolism. While the roles of CLR and BAs in regulating metabolism and tissue function are well known, research of the last two decades revealed the existence of specific protein receptors for CLR or BAs in tissues with minor contribution to lipid metabolism, raising the possibility that these lipids serve as signaling molecules throughout the body...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28860314/dynamic-regulation-of-the-subunit-composition-of-bk-channels-in-smooth-muscle
#15
EDITORIAL
Gregory M Dick, Johnathan D Tune
No abstract text is available yet for this article.
September 1, 2017: Circulation Research
https://www.readbyqxmd.com/read/28858616/inferior-olivary-tmem16b-mediates-cerebellar-motor-learning
#16
Yang Zhang, Zhushan Zhang, Shaohua Xiao, Jason Tien, Son Le, Trieu Le, Lily Y Jan, Huanghe Yang
Ca(2+)-activated ion channels shape membrane excitability and Ca(2+) dynamics in response to cytoplasmic Ca(2+) elevation. Compared to the Ca(2+)-activated K(+) channels, known as BK and SK channels, the physiological importance of Ca(2+)-activated Cl(-) channels (CaCCs) in neurons has been largely overlooked. Here we report that CaCCs coexist with BK and SK channels in inferior olivary (IO) neurons that send climbing fibers to innervate cerebellar Purkinje cells for the control of motor learning and timing...
August 30, 2017: Neuron
https://www.readbyqxmd.com/read/28838128/hypoxia-sensing-in-plants-on-a-quest-for-ion-channels-as-putative-oxygen-sensors
#17
Feifei Wang, Zhong-Hua Chen, Sergey Shabala
Over 17 million km2 of land is affected by soil flooding every year, resulting in substantial yield losses and jeopardizing food security across the globe. A key step in resolving this problem and creating stress-tolerant cultivars is an understanding of the mechanisms by which plants sense low-oxygen stress. In this work, we review the current knowledge about the oxygen-sensing and signaling pathway in mammalian and plant systems and postulate the potential role of ion channels as putative oxygen sensors in plant roots...
July 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28830977/lack-of-direct-effect-of-adiponectin-on-vascular-smooth-muscle-cell-bkca-channels-or-ca-2-signaling-in-the-regulation-of-small-artery-pressure-induced-constriction
#18
Rachael Baylie, Majid Ahmed, Adrian D Bonev, David C Hill-Eubanks, Thomas J Heppner, Mark T Nelson, Adam S Greenstein
The aim of this study was to investigate mechanisms by which adiponectin influences vascular Ca(2+) signaling, K(+) channel activity and thus contractile tone of small arteries. Vasodilation to adiponectin was studied in mesenteric resistance arteries constricted with intraluminal pressure. Ca(2+) signals were characterized using high speed confocal microscopy of intact arteries. Patch clamp investigated the effect of adiponectin on individual VSMC potassium (K(+)) channel currents. Adiponectin dilated arteries constricted with pressure-induced tone by approximately 5% and the induced vasodilation was only transient...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28818302/mitochondrial-ca-2-activated-k-channels-and-their-role-in-cell-life-and-death-pathways
#19
REVIEW
Inge E Krabbendam, Birgit Honrath, Carsten Culmsee, Amalia M Dolga
Ca(2+)-activated K(+) channels (KCa) are expressed at the plasma membrane and in cellular organelles. Expression of all KCa channel subtypes (BK, IK and SK) has been detected at the inner mitochondrial membrane of several cell types. Primary functions of these mitochondrial KCa channels include the regulation of mitochondrial ROS production, maintenance of the mitochondrial membrane potential and preservation of mitochondrial calcium homeostasis. These channels are therefore thought to contribute to cellular protection against oxidative stress through mitochondrial mechanisms of preconditioning...
July 22, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28754781/nongenomic-modulation-of-the-large-conductance-voltage-and-ca-2-activated-k-channels-by-estrogen-a-novel-regulatory-mechanism-in-human-detrusor-smooth-muscle
#20
Kiril L Hristov, Shankar P Parajuli, Aaron Provence, Eric S Rovner, Georgi V Petkov
Estrogens have an important role in regulating detrusor smooth muscle (DSM) function. However, the underlying molecular and cellular mechanisms by which estrogens control human DSM excitability and contractility are not well known. Here, we used human DSM specimens from open bladder surgeries on 27 patients to elucidate the mechanism by which 17β-estradiol regulates large conductance voltage- and Ca(2+)-activated K(+) (BK) channels, the most prominent K(+) channels in human DSM We employed single BK channel recordings on inside-out excised membrane patches, perforated whole-cell patch-clamp on freshly isolated DSM cells, and isometric tension recordings on DSM-isolated strips to investigate the mechanism by which 17β-estradiol activates BK channels...
July 2017: Physiological Reports
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