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https://www.readbyqxmd.com/read/28322838/effect-of-antiarrhythmic-drugs-on-small-conductance-calcium-activated-potassium-channels
#1
Rafel Simó Vicens, Daniel R P Sauter, Morten Grunnet, Jonas G Diness, Bo H Bentzen
Atrial fibrillation (AF) is the most common type of arrhythmia. Current pharmacological treatment for AF is moderately effective and/or increases the risk of serious ventricular adverse effects. To avoid ventricular adverse effects, a new target has been considered, the small conductance calcium-activated K(+) channels (KCa2.X, SK channels). In the heart, KCa2.X channels are functionally more important in atria compared to ventricles, and pharmacological inhibition of the channel confers atrial selective prolongation of the cardiac action potential and converts AF to sinus rhythm in animal models of AF...
March 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#2
Timur A Mavlyutov, Erin M Baker, Tasher M Losenegger, Jaimie R Kim, Brian Torres, Miles L Epstein, Arnold E Ruoho
The membrane bound 223 amino acid Sigma-1 Receptor (S1R) serves as a molecular chaperone and functional regulator of many signaling proteins. Spinal cord motor neuron activation occurs, in part, via large ventral horn cholinergic synapses called C-boutons/C-terminals. Chronic excitation of motor neurons and alterations in C-terminals has been associated with Amyotrophic Lateral Sclerosis (ALS ). The S1R has an important role in regulating motor neuron function. High levels of the S1R are localized in postsynaptic endoplasmic reticulum (ER) subsurface cisternae within 10-20 nm of the plasma membrane that contain muscarinic type 2 acetylcholine receptors (M2AChR), calcium activated potassium channels (Kv2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28294142/inosine-attenuates-spontaneous-activity-in-the-rat-neurogenic-bladder-through-an-a2b-pathway
#3
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/28285409/pharmacological-blockade-of-small-conductance-ca-2-activated-k-channels-by-ica-reduces-arrhythmic-load-in-rats-with-acute-myocardial-infarction
#4
Laura A Hundahl, Stefan M Sattler, Lasse Skibsbye, Jonas G Diness, Jacob Tfelt-Hansen, Thomas Jespersen
Acute myocardial infarction (AMI) with development of ventricular fibrillation (VF) is a common cause of sudden cardiac death (SCD). At present, no pharmacological treatment has successfully been able to prevent VF in the acute stage of AMI. This study investigates the antiarrhythmic effect of inhibiting small conductance Ca(2+)-activated K(+) (SK) channels using the pore blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) in AMI rats. Acute coronary ligation was performed in 26 anesthetized rats, and ECG, monophasic action potentials (MAPs), and ventricular effective refractory period (vERP) were recorded...
March 11, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28282037/sk2-channels-regulate-mitochondrial-respiration-and-mitochondrial-ca-2-uptake
#5
Birgit Honrath, Lina Matschke, Tammo Meyer, Lena Magerhans, Fabiana Perocchi, Goutham K Ganjam, Hans Zischka, Cornelius Krasel, Albert Gerding, Barbara M Bakker, Moritz Bünemann, Stefan Strack, Niels Decher, Carsten Culmsee, Amalia M Dolga
Mitochondrial calcium ([Ca(2+)]m) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca(2+)]m uptake upon SK channel activation as detected by time lapse mitochondrial Ca(2+) measurements with the Ca(2+)-binding mitochondria-targeted aequorin and FRET-based [Ca(2+)]m probes...
March 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28280420/chronic-ca-2-influx-through-voltage-dependent-ca-2-channels-enhance-delayed-rectifier-k-currents-via-activating-src-family-tyrosine-kinase-in-rat-hippocampal-neurons
#6
Yoon-Sil Yang, Sang-Chan Jeon, Dong-Kwan Kim, Su-Yong Eun, Sung-Cherl Jung
Excessive influx and the subsequent rapid cytosolic elevation of Ca(2+) in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca(2+) level in normal as well as pathological conditions. Delayed rectifier K(+) channels (IDR channels) play a role to suppress membrane excitability by inducing K(+) outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca(2+)-mediated excitotoxic conditions...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28277938/sk-channel-subtypes-enable-parallel-optimized-coding-of-behaviorally-relevant-stimulus-attributes-a-review
#7
Chengjie G Huang, Maurice J Chacron
Ion channels play essential roles towards determining how neurons respond to sensory input in order to mediate perception and behavior. Small conductance calcium-activated potassium (SK) channels are found ubiquitously throughout the brain and have been extensively characterized both molecularly and physiologically in terms of structure and function. It is clear that SK channels are key determinants of neural excitability as they mediate important neuronal response properties such as spike frequency adaptation...
March 1, 2017: Channels
https://www.readbyqxmd.com/read/28262027/bis-15-crown-5-ether-pillar-5-arene-k-responsive-channels
#8
Wei-Xu Feng, Zhanhu Sun, Yan Zhang, Yves-Marie Legrand, Eddy Petit, Cheng-Yong Su, Mihail Barboiu
An artificial selective K(+) channel is formed from the supramolecular organization on bis(benzo-15-crown-5- ether-ureido)-pillar[5]arene compound. This channel achieves a selectivity of SK(+)/Na(+) = 5 for an initial transport rate of kK(+) = 3.2 × 10(-3) s(-1). The cation-file diffusion occurs via selective macrocyclic-filters anchored on inactive supporting pillar[5]arene relays. The sandwich-type binding geometry of the K(+) cation by two 15-crown-5 moieties sites is a key feature influencing channel efficiency...
March 6, 2017: Organic Letters
https://www.readbyqxmd.com/read/28208379/prediction-of-the-moments-in-advection-diffusion-lattice-boltzmann-method-i-truncation-dispersion-skewness-and-kurtosis
#9
Irina Ginzburg
The effect of the heterogeneity in the soil structure or the nonuniformity of the velocity field on the modeled resident time distribution (RTD) and breakthrough curves is quantified by their moments. While the first moment provides the effective velocity, the second moment is related to the longitudinal dispersion coefficient (k_{T}) in the developed Taylor regime; the third and fourth moments are characterized by their normalized values skewness (Sk) and kurtosis (Ku), respectively. The purpose of this investigation is to examine the role of the truncation corrections of the numerical scheme in k_{T}, Sk, and Ku because of their interference with the second moment, in the form of the numerical dispersion, and in the higher-order moments, by their definition...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28162597/-355-riluzole-actions-on-sk-channels-in-the-amygdala-in-acute-arthritic-and-chronic-neuropathic-pain
#10
J Thompson, G Ji, V Neugebauer
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28115487/cholinergic-interneurons-underlie-spontaneous-dopamine-release-in-nucleus-accumbens
#11
Jordan T Yorgason, Douglas M Zeppenfeld, John T Williams
The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine...
February 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28108814/the-small-neurotoxin-apamin-blocks-not-only-small-conductance-ca-2-activated-k-channels-sk-type-but-also-the-voltage-dependent-kv1-3-channel
#12
Patrick Voos, Mehtap Yazar, René Lautenschläger, Oliver Rauh, Anna Moroni, Gerhard Thiel
Apamin is frequently used as a specific blocker of small-conductance Ca(2+)-activated (SK type) K(+) channels. Here we show that the small neurotoxin is not as specific as anticipated. It is also a high-affinity inhibitor with an IC50 of 13 nM of the Kv1.3 channel; it blocks the latter with potency similar to the Kv1.3 blocker PAP-1. Since SK type channels and Kv1.3 channels are frequently coexpressed in different tissues such as cells of the immune system, apamin must be used with caution as a pharmacological tool...
January 20, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28096168/sk-channel-enhancers-attenuate-ca2-dependent-arrhythmia-in-hypertrophic-hearts-by-regulating-mito-ros-dependent-oxidation-and-activity-of-ryr
#13
Tae Yun Kim, Radmila Terentyeva, Karim H F Roder, Weiyan Li, Man Liu, Ian Greener, Shanna Hamilton, Iuliia Polina, Kevin R Murphy, Richard T Clements, Samuel C Dudley, Gideon Koren, Bum-Rak Choi, Dmitry Terentyev
AIM: s: Plasmamembrane small conductance Ca<su2+p>-activated K<su+ p > (SK) channels were implicated in ventricular arrhythmias in infarcted and failing hearts. Recently, SK channels were detected in the mitochondria inner membrane (mSK), and their activation protected from acute ischemia-reperfusion injury by reducing intracellular levels of reactive oxygen species (ROS). We hypothesized that mSK play an important role in regulating mitochondrial function in chronic cardiac diseases...
January 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28093473/differential-regulation-of-nmda-receptor-mediated-transmission-by-sk-channels-underlies-dorsal-ventral-differences-in-dynamics-of-schaffer-collateral-synaptic-function
#14
Walter E Babiec, Shekib A Jami, Ryan Guglietta, Patrick B Chen, Thomas J O'Dell
Behavioral, physiological, and anatomical evidence indicates that the dorsal and ventral zones of the hippocampus have distinct roles in cognition. How the unique functions of these zones might depend on differences in synaptic and neuronal function arising from the strikingly different gene expression profiles exhibited by dorsal and ventral CA1 pyramidal cells is unclear. To begin to address this question, we investigated the mechanisms underlying differences in synaptic transmission and plasticity at dorsal and ventral Schaffer collateral (SC) synapses in the mouse hippocampus...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28089668/ebio-does-not-induce-cardiomyogenesis-in-human-pluripotent-stem-cells-but-modulates-cardiac-subtype-enrichment-by-lineage-selective-survival
#15
Monica Jara-Avaca, Henning Kempf, Michael Rückert, Diana Robles-Diaz, Annika Franke, Jeanne de la Roche, Martin Fischer, Daniela Malan, Philipp Sasse, Wladimir Solodenko, Gerald Dräger, Andreas Kirschning, Ulrich Martin, Robert Zweigerdt
Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca(2+)-activated potassium channels (SKs 1-4). Investigating EBIO in human pluripotent stem cells (PSCs), we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28065942/neuregulin-1-erbb-module-in-c-bouton-synapses-on-somatic-motor-neurons-molecular-compartmentation-and-response-to-peripheral-nerve-injury
#16
Anna Casanovas, Sara Salvany, Víctor Lahoz, Olga Tarabal, Lídia Piedrafita, Raimundo Sabater, Sara Hernández, Jordi Calderó, Josep E Esquerda
The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28050270/downregulation-of-purkinje-cell-activity-by-modulators-of-small-conductance-calcium-activated-potassium-channels-in-rat-cerebellum
#17
T V Karelina, Yu D Stepanenko, P A Abushik, D A Sibarov, S M Antonov
Small-conductance calcium-activated potassium channels (SK channels) are widely expressed in CNS tissues. Their functions, however, have not been well studied. Participation of SK channels in Purkinje cell (PC) pacemaker activity has been studied predominantly in vitro. Here we studied for the first time the effects of SK channel activation by NS309 or CyPPA on the PC simple spike frequency in vivo in adult (3 - 6 months) and aged (22 - 28 months) rats using extracellular microelectrode recordings. Both pharmacological agents caused a statistically significant decrease in the PC simple spike frequency...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28049949/differential-contribution-of-nerve-derived-noradrenaline-to-high-k-induced-contraction-depending-on-type-of-artery
#18
Hirotake Ishida, Shin-Ya Saito, Eita Hishinuma, Tomohisa Ishikawa
High K(+)-induced contraction of arterial smooth muscle is thought to be mediated by membrane depolarization and subsequent activation of voltage-dependent Ca(2+) channels (VDCCs). In line with this, this study found that contraction induced by 80 mM K(+) was almost abolished by nifedipine (1 µM), a VDCC inhibitor, in isolated rat aorta, and was markedly suppressed in the iliac artery. However, nifedipine (1 µM) only partially suppressed high K(+)-induced contraction in the tail artery. The contractions remaining in the arteries were further reduced by non-selective cation channel (NSCC) inhibitors, including 2-aminoethoxydiphenyl borate (2-APB) (100 µM), SK&F96365 (10 µM), and 3,4-dihydro-6,7-dimethoxy-α-phenyl-N,N-bis[2-(2,3,4-trimethoxyphenyl)ethyl]-1-isoquinolineacetamide hydrochloride (LOE908) (10 µM)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28026020/low-pho-boosts-burst-firing-and-catecholamine-release-by-blocking-task-1-and-bk-channels-while-preserving-cav1-channels-in-mouse-chromaffin-cells
#19
Laura Guarina, David H F Vandael, Valentina Carabelli, Emilio Carbone
Mouse chromaffin cells (MCCs) generate action potential (AP) firing that regulates the Ca(2+) -dependent release of catecholamines (CAs). Recent findings indicate that MCCs possess a variety of spontaneous firing modes that span from the common "tonic-irregular" to the less frequent "burst" firing. This latter is evident in a small fraction of MCCs but occurs regularly when Nav1.3/1.7 channels are made less available or when the Slo1β2-subunit responsible for BK channel inactivation is deleted. Burst firing causes massive increases of Ca(2+) -entry and potentiates CA release ∼3...
December 27, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/28008669/r-type-ca-2-channels-couple-to-inhibitory-neurotransmission-to-the-longitudinal-muscle-in-the-guinea-pig-ileum
#20
Eileen S Rodriguez-Tapia, Vinogran Naidoo, Matthew DeVries, Alberto Perez-Medina, James J Galligan
What is the central question of this study? Subtypes of enteric neurons are coded by the neurotransmitters they synthesize, but it is not known whether enteric neuron subtypes might also be coded by other proteins, including calcium channel subtypes controlling neurotransmitter release. What is the main finding and its importance? Our data indicate that guinea-pig ileum myenteric neuron subtypes may be coded by calcium channel subtypes. We found that R-type calcium channels are expressed by inhibitory but not excitatory longitudinal muscle motoneurons...
March 1, 2017: Experimental Physiology
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