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https://www.readbyqxmd.com/read/29160573/activation-of-voltage-dependent-k-channels-strongly-limits-hypoxia-induced-elevation-of-ca-2-i-in-rat-carotid-body-glomus-cells
#1
Jiaju Wang, Donghee Kim
Large-conductance KCa (BK) and other voltage-dependent K(+) channels (Kv) are highly expressed in carotid body (CB) glomus cells, but their role in hypoxia-induced excitation is still not well defined and remains controversial. We addressed this issue by studying the effects of inhibitors of BK (IBTX) and BK/Kv (TEA/4-AP) on [Ca(2+) ]i responses to a wide range of hypoxia at different levels of resting cell Em. IBTX and TEA/4-AP did not affect the basal [Ca(2+) ]i in isolated glomus cells bathed in 5 mm KClo , but elicited transient increases in [Ca(2+) ]i in cells that were moderately depolarized (11-20 mV) by elevation of [KCl]o (12-20 mm)...
November 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29152668/the-role-of-astrocytic-calcium-and-trpv4-channels-in-neurovascular-coupling
#2
Allanah Kenny, Michael J Plank, Tim David
Neuronal activity evokes a localised change in cerebral blood flow in a response known as neurovascular coupling (NVC). Although NVC has been widely studied the exact mechanisms that mediate this response remain unclear; in particular the role of astrocytic calcium is controversial. Mathematical modelling can be a useful tool for investigating the contribution of various signalling pathways towards NVC and for analysing the underlying cellular mechanisms. The lumped parameter model of a neurovascular unit with both potassium and nitric oxide (NO) signalling pathways and comprised of neurons, astrocytes, and vascular cells has been extended to include the glutamate induced astrocytic calcium pathway with epoxyeicosatrienoic acid (EET) signalling and the stretch dependent TRPV4 calcium channel on the astrocytic endfoot...
November 20, 2017: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/29145442/downregulation-of-kcnmb4-expression-and-changes-in-bk-channel-subtype-in-hippocampal-granule-neurons-following-seizure-activity
#3
Luke E Whitmire, Ling Ling, Vladslav Bugay, Chase M Carver, Santosh Timilsina, Hui-Hsiu Chuang, David B Jaffe, Mark S Shapiro, Jose E Cavazos, Robert Brenner
A major challenge is to understand maladaptive changes in ion channels that sets neurons on a course towards epilepsy development. Voltage- and calcium-activated K+ (BK) channels contribute to early spike timing in neurons, and studies indicate that the BK channel plays a pathological role in increasing excitability early after a seizure. Here, we have investigated changes in BK channels and their accessory β4 subunit (KCNMB4) in dentate gyrus (DG) granule neurons of the hippocampus, key neurons that regulate excitability of the hippocampus circuit...
2017: PloS One
https://www.readbyqxmd.com/read/29144974/double-nanodomain-coupling-of-calcium-channels-ryanodine-receptors-and-bk-channels-controls-the-generation-of-burst-firing
#4
Tomohiko Irie, Laurence O Trussell
Action potentials clustered into high-frequency bursts play distinct roles in neural computations. However, little is known about ionic currents that control the duration and probability of these bursts. We found that, in cartwheel inhibitory interneurons of the dorsal cochlear nucleus, the likelihood of bursts and the interval between their spikelets were controlled by Ca(2+) acting across two nanodomains, one between plasma membrane P/Q Ca(2+) channels and endoplasmic reticulum (ER) ryanodine receptors and another between ryanodine receptors and large-conductance, voltage- and Ca(2+)-activated K(+) (BK) channels...
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29136290/the-role-of-ca-2-dependent-k-channels-at-the-rat-corticostriatal-synapses-revealed-by-paired-pulse-stimulation
#5
Angel A Robles G, Ana V Vega, Carolina Gonzalez-Sandoval, Jaime Barral
Potassium channels play an important role in modulating synaptic activity both at presynaptic and postsynaptic levels. We have shown before that presynaptically located KV and KIR channels modulate the strength of corticostriatal synapses in rat brain, but the role of other types of potassium channels at these synapses remains largely unknown. Here we show that calcium-dependent potassium channels BK-type but not SK-type channels are located presynaptically in corticostriatal synapses. We stimulated cortical neurons in rat brain slices and recorded postsynaptic excitatory potentials (EPSP) in medium spiny neurons (MSN) in dorsal neostriatum...
November 14, 2017: Synapse
https://www.readbyqxmd.com/read/29051185/cgmp-elevating-compounds-and-ischemic-conditioning-provide-cardioprotection-against-ischemia-and-reperfusion-injury-via-cardiomyocyte-specific-bk-channels
#6
Sandra Frankenreiter, Piotr Bednarczyk, Angelina Kniess, Nadja Bork, Julia Straubinger, Piotr Koprowski, Antoni Wrzosek, Eva Mohr, Angela Logan, Michael P Murphy, Meinrad Gawaz, Thomas Krieg, Adam Szewczyk, Viacheslav O Nikolaev, Peter Ruth, Robert Lukowski
Background -The nitric oxide-sensitive guanylyl cyclase (NO-GC)/cyclic guanosine-3',5'-monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI)-signaling pathway can afford protection against the ischemia and reperfusion (I/R) injury that occurs during myocardial infarction (MI). Reportedly, voltage and Ca(2+)-activated K(+) channels of the BK-type are stimulated by cGMP/cGKI and recent ex-vivo studies implicated that increased BK activity favors the survival of the myocardium at I/R. It remains unclear, however, whether the molecular events downstream of cGMP involve BK channels present in cardiomyocytes (CMs) or in other cardiac cell types...
October 19, 2017: Circulation
https://www.readbyqxmd.com/read/29050967/role-of-k-channels-in-regulating-spontaneous-activity-in-the-muscularis-mucosae-of-guinea-pig-bladder
#7
Ken Lee, Ayu Isogai, Minori Antoh, Shunichi Kajioka, Masatoshi Eto, Hikaru Hashitani
To explore the roles of various K(+) channels in regulating the spontaneous activity of bladder muscularis mucosae (MM) that is considered to play an important role in maintaining mucosal function. Effects of K(+) channel modulators on electrical and contractile activity in the guinea-pig bladder MM were examined using intracellular microelectrode and isometric tension recording. The MM predominately generated bursting spontaneous action potentials (SAPs) and phasic contractions (SPCs) that were blocked by nifedipine (1µM)...
October 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29040972/regulation-of-coronary-arterial-large-conductance-ca2-activated-k-channel-protein-expression-and-function-by-n-3-polyunsaturated-fatty-acids-in-diabetic-rats
#8
Xu Tang, Ling-Ling Qian, Ru-Xing Wang, Yong Yao, Shi-Peng Dang, Ying Wu, Wen Wang, Yuan Ji, Man-Qing Sun, Da-Yun Xia, Xiao-Yu Liu, Dai-Min Zhang, Qiang Chai, Tong Lu
AIM: The objective of this study was to examine the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on coronary arterial large conductance Ca2+-activated K+ (BK) channel function in coronary smooth muscle cells (SMCs) of streptozotocin-induced diabetic rats. METHODS: The effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on coronary BK channel open probabilities were determined using the patch clamp technique. The mRNA and protein expressions of BK channel subunits were measured using qRT-PCR and Western blots...
October 18, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/29025867/threading-the-biophysics-of-mammalian-slo1-channels-onto-structures-of-an-invertebrate-slo1-channel
#9
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...
November 6, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29016852/potassium-channel-dysfunction-underlies-purkinje-neuron-spiking-abnormalities-in-spinocerebellar-ataxia-type-2
#10
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
#11
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
#12
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
#13
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 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28955251/molecular-mechanisms-underlying-renin-angiotensin-aldosterone-system-mediated-regulation-of-bk-channels
#14
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
#15
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
#16
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...
December 4, 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
#17
Guruprasad Kuntamallappanavar, Alex M Dopico
BACKGROUND AND PURPOSE: Ethanol at concentrations obtained in the 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 K(+) (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
#18
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
#19
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
#20
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
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