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"ryanodine receptor" OR "ryr" OR "ryr2"

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https://www.readbyqxmd.com/read/29352041/stress-signaling-jnk2-crosstalk-with-camkii-underlies-enhanced-atrial-arrhythmogenesis
#1
Jiajie Yan, Weiwei Zhao, Justin K Thomson, Xianlong Gao, Dominic M DeMarco, Elena Carrillo, Biyi Chen, Xiaomin Wu, Kenneth S Ginsburg, Mamdouh Bakhos, Donald M Bers, Mark E Anderson, Long-Sheng Song, Michael Fill, Xun Ai
Rationale: Atrial fibrillation (AF) is the most common arrhythmia and advanced age is an inevitable and predominant AF risk factor. However, the mechanisms that couple aging and AF propensity remain unclear, making targeted therapeutic interventions unattainable. Objective: To explore the functional role of an important stress-response c-Jun N-terminal kinase (JNK) in sarcoplasmic reticulum (SR) Ca2+ handling and consequently Ca2+-mediated atrial arrhythmias. Methods and Results: We employed a series of cutting-edge electrophysiological and molecular techniques, exploited the power of transgenic mouse models to detail the molecular mechanism, and verified its clinical applicability in parallel studies on donor human hearts...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29350269/exome-analysis-in-34-sudden-unexplained-death-sud-victims-mainly-identified-variants-in-channelopathy-associated-genes
#2
Jacqueline Neubauer, Maria Rita Lecca, Giancarlo Russo, Christine Bartsch, Argelia Medeiros-Domingo, Wolfgang Berger, Cordula Haas
Sudden cardiac death (SCD) is one of the major causes of mortality worldwide, mostly involving coronary artery disease in the elderly. In contrary, sudden death events in young victims often represent the first manifestation of undetected genetic cardiac diseases, which remained without any symptoms during lifetime. Approximately 30% of these sudden death cases have no definite cardiac etiology after a comprehensive medicolegal investigation and are therefore termed as sudden unexplained death (SUD) cases. Advances in high-throughput sequencing approaches have provided an efficient diagnostic tool to identify likely pathogenic variants in cardiovascular disease-associated genes in otherwise autopsy-negative SUD cases...
January 19, 2018: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/29337220/botaf-a-new-buthus-occitanus-tunetanus-scorpion-toxin-produces-potent-analgesia-in-rodents
#3
Riadh Maatoug, Jed Jebali, Régis Guieu, Michel De Waard, Riadh Kharrat
This work reports the purification of new potent scorpion neuropeptide, named BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain peptide that shares very high similarity with the original β-like scorpion toxin group, in which several peptides have been characterized to be anti-nociceptive in rodents. BotAF administration to rodents does not produce any toxicity or motor impairment, including at high doses. In all models investigated, BotAF turned out to be an efficient peptide in abolishing acute and inflammatory (both somatic and visceral) pain in rodents...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29320748/true-molecular-scale-visualization-of-variable-clustering-properties-of-ryanodine-receptors
#4
Isuru Jayasinghe, Alexander H Clowsley, Ruisheng Lin, Tobias Lutz, Carl Harrison, Ellen Green, David Baddeley, Lorenzo Di Michele, Christian Soeller
Signaling nanodomains rely on spatial organization of proteins to allow controlled intracellular signaling. Examples include calcium release sites of cardiomyocytes where ryanodine receptors (RyRs) are clustered with their molecular partners. Localization microscopy has been crucial to visualizing these nanodomains but has been limited by brightness of markers, restricting the resolution and quantification of individual proteins clustered within. Harnessing the remarkable localization precision of DNA-PAINT (<10 nm), we visualized punctate labeling within these nanodomains, confirmed as single RyRs...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29315676/aging-impairs-regulation-of-ryanodine-receptors-from-edl-but-not-soleus-muscles
#5
Angela J Gaboardi, Jochen Kressler, Teresa K Snow, Edward M Balog
INTRODUCTION: Because impaired excitation-contraction coupling and reduced sarcoplasmic reticulum Ca2+ release may contribute to the age-associated decline in skeletal muscle strength, we investigated the effect of aging on RyR1 regulation by physiological channel ligands. METHODS: [3 H]Ryanodine binding to membranes from 8 and 26 month old Fischer 344 extensor digitorum longus (EDL) and soleus muscles was used to investigate the effects of age on RyR1 modulation by Ca2+ and calmodulin (CaM)...
January 9, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29314443/ryanodine-receptor-inhibition-by-dantrolene-effectively-suppresses-ventricular-arrhythmias-in-an-ex-vivo-model-of-long-qt-syndrome
#6
Gerrit Frommeyer, Julius Krawczyk, Christian Ellermann, Nils Bögeholz, Simon Kochhäuser, Dirk G Dechering, Michael Fehr, Lars Eckardt
AIMS: A significant antiarrhythmic potential of ryanodine receptor inhibition was reported in experimental studies. The aim of the present study was to assess potential antiarrhythmic effects of dantrolene in an experimental whole-heart model of drug-induced long-QT syndrome (LQTS). METHODS: In 12 isolated rabbit hearts long-QT-2-syndrome was simulated by infusion of erythromycin (300μM). 12 rabbit hearts were treated with veratridine (0.5μM) to mimic long-QT-3-syndrome...
January 4, 2018: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/29298851/atypical-periodic-paralysis-and-myalgia-a-novel-ryr1-phenotype
#7
Emma Matthews, Christoph Neuwirth, Fatima Jaffer, Renata S Scalco, Doreen Fialho, Matt Parton, Dipa Raja Rayan, Karen Suetterlin, Richa Sud, Roland Spiegel, Rachel Mein, Henry Houlden, Andrew Schaefer, Estelle Healy, Jacqueline Palace, Ros Quinlivan, Susan Treves, Janice L Holton, Heinz Jungbluth, Michael G Hanna
OBJECTIVE: To characterize the phenotype of patients with symptoms of periodic paralysis (PP) and ryanodine receptor (RYR1) gene mutations. METHODS: Cases with a possible diagnosis of PP but additional clinicopathologic findings previously associated with RYR1-related disorders were referred for a tertiary neuromuscular clinical assessment in which they underwent detailed clinical evaluation, including neurophysiologic assessment, muscle biopsy, and muscle MRI. Genetic analysis with next-generation sequencing and/or targeted Sanger sequencing was performed...
January 3, 2018: Neurology
https://www.readbyqxmd.com/read/29288034/structural-and-functional-remodelling-of-the-atrioventricular-node-with-ageing-in-rats-the-role-of-hyperpolarization-activated-cyclic-nucleotide-gated-and-ryanodine-2-channels
#8
Yawer Saeed, Ian Temple, Zoltan Borbas, Andrew Atkinson, Joseph Yanni, Michal Maczewski, Urszula Mackiewicz, Mariam Aly, Sunil J R J Logantha, Clifford Garratt, Halina Dobrzynski
BACKGROUND: Ageing is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVES: The aim of the study is to identify the structural and functional remodelling in the atrioventricular junction (AVJ) with ageing. METHODS: Electrophysiological, histology and immunohistochemistry experiments on male Wistar-Hanover rats aged 3months (n=24) and 2years (n=15) were performed. AH interval, Wenkebach cycle length (WBCL) and AVN effective refractory period (AVNERP) were measured...
December 26, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29284662/junctional-trafficking-and-restoration-of-retrograde-signaling-by-the-cytoplasmic-ryr1-domain
#9
Alexander Polster, Stefano Perni, Dilyana Filipova, Ong Moua, Joshua D Ohrtman, Hicham Bichraoui, Kurt G Beam, Symeon Papadopoulos
The type 1 ryanodine receptor (RyR1) in skeletal muscle is a homotetrameric protein that releases Ca2+ from the sarcoplasmic reticulum (SR) in response to an "orthograde" signal from the dihydropyridine receptor (DHPR) in the plasma membrane (PM). Additionally, a "retrograde" signal from RyR1 increases the amplitude of the Ca2+ current produced by CaV1.1, the principle subunit of the DHPR. This bidirectional signaling is thought to depend on physical links, of unknown identity, between the DHPR and RyR1. Here, we investigate whether the isolated cytoplasmic domain of RyR1 can interact structurally or functionally with CaV1...
December 28, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29280435/transcription-factor-dependent-enhancer-transcription-defines-a-gene-regulatory-network-for-cardiac-rhythm
#10
Xinan H Yang, Rangarajan D Nadadur, Catharina Re Hilvering, Valerio Bianchi, Michael Werner, Stefan R Mazurek, Margaret Gadek, Kaitlyn M Shen, Joseph Aaron Goldman, Leonid Tyan, Jenna Bekeny, Johnathan M Hall, Nutishia Lee, Carlos Perez-Cervantes, Ozanna Burnicka-Turek, Kenneth D Poss, Christopher R Weber, Wouter de Laat, Alexander J Ruthenburg, Ivan P Moskowitz
The noncoding genome is pervasively transcribed. Noncoding RNAs (ncRNAs) generated from enhancers have been proposed as a general facet of enhancer function and some have been shown to be required for enhancer activity. Here we examine the transcription-factor-(TF)-dependence of ncRNA expression to define enhancers and enhancer-associated ncRNAs that are involved in a TF-dependent regulatory network. TBX5, a cardiac TF, regulates a network of cardiac channel genes to maintain cardiac rhythm. We deep sequenced wildtype and Tbx5-mutant mouse atria, identifying ~2600 novel Tbx5-dependent ncRNAs...
December 27, 2017: ELife
https://www.readbyqxmd.com/read/29279414/t-tubule-remodeling-and-increased-heterogeneity-of-calcium-release-during-the-progression-to-heart-failure-in-intact-rat-ventricle
#11
Jasleen K Singh, Varderes Barsegyan, Nikhil Bassi, William Marszalec, Shannon Tai, Shruthi Mothkur, Maaz Mulla, Elsa Nico, Yohannes Shiferaw, Gary L Aistrup, John Andrew Wasserstrom
A highly organized transverse-tubule (TT) system is essential to normal Ca2+ cycling and cardiac function. We explored the relationship between the progressive disruption of TTs and resulting Ca2+ cycling during the development of heart failure (HF). Confocal imaging was used to measure Ca2+ transients and 2-D z-stack images in left ventricular epicardial myocytes of intact hearts from spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats. TT organization was measured as the organizational index (OI) derived from a fast Fourier transform of TT organization...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29278865/simvastatin-activates-single-skeletal-ryr1-channels-but-exerts-more-complex-regulation-of-the-cardiac-ryr2-isoform
#12
Elisa Venturi, Chris Lindsay, Sabine Lotteau, Zhaokang Yang, Emma Steer, Katja Witschas, Abigail D Wilson, James R Wickens, Angela J Russell, Derek Steele, Sarah Calaghan, Rebecca Sitsapesan
BACKGROUND AND PURPOSE: Statins are amongst the most widely prescribed drugs for those at risk of cardiovascular disease, lowering cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Although effective in prevention of cardiovascular disease, statin use is associated with muscle weakness, myopathies and, in rare cases, fatal rhabdomyolysis. As simvastatin, a commonly prescribed statin, can promote Ca2+ release from sarcoplasmic reticulum (SR) vesicles, we investigated if simvastatin could directly activate skeletal (RyR1) and cardiac (RyR2) ryanodine receptors...
December 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29278207/omecamtiv-mecarbil-a-myosin-motor-activator-agent-with-promising-clinical-performance-and-new-in-vitro-results
#13
Peter Nanasi, Istvan Komaromi, Marta Gaburjakova, Janos Almassy
Clinical treatment of heart failure is still suffering from limited efficacy and unfavorable side effects. The recently developed group of agents, the myosin motor activators, act directly on cardiac myosin resulting in an increased force generation and prolongation of contraction. The lead molecule, omecamtiv mecarbil is now in human phase 3. In addition to the promising clinical data published so far, there are new in vitro results indicating that the effect of omecamtiv mecarbil on contractility is rate-dependent...
December 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29251109/human-olfactory-ensheathing-cell-transplantation-improves-motor-function-in-a-mouse-model-of-type-3-spinocerebellar-ataxia
#14
Jeanne Hsieh, Jen-Wei Liu, Horng-Jyh Harn, Kuo-Wei Hsueh, Karthyayani Rajamani, Yu-Chen Deng, Chih-Min Chia, Woei-Cheang Shyu, Shinn-Zong Lin, Tzyy-Wen Chiou
Spinocerebellar ataxia (SCA) is a progressive neurodegenerative disease that affects the cerebellum and spinal cord. Among the 40 types of SCA, SCA type 3 (SCA3), also referred to as Machado-Joseph disease, is the most common. In the present study, we investigated the therapeutic effects of intracranial transplantation of human olfactory ensheathing cells (hOECs) in the ATXN3-84Q mouse model of SCA3. Motor function begins to decline in ATXN3-84Q transgenic mice at approximately 13 weeks of age. ATXN3-84Q mice that received intracranial hOEC transplantation into the dorsal raphe nucleus of the brain exhibited significant improvements in motor function, as measured by the rotarod performance test and footprint pattern analysis...
October 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29248564/el20-a-potent-antiarrhythmic-compound-selectively-inhibits-calmodulin-deficient-ryanodine-receptor-type-2
#15
Robert C Klipp, Na Li, Qiongling Wang, Tarah A Word, Martha Sibrian-Vazquez, Robert M Strongin, Xander H T Wehrens, Jonathan J Abramson
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disorder caused by mutations in the cardiac ryanodine receptor (RyR2) that increase diastolic Ca2+ leak from the sarcoplasmic reticulum (SR). Calmodulin (CaM) dissociation from RyR2 has been associated with diastolic Ca2+ leak in heart failure. OBJECTIVE: Determine if tetracaine-derivative, EL20, inhibits abnormal Ca2+ release from RyR2 in a CPVT model and the underlying mechanism of inhibition...
December 14, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29247050/voltage-modulates-halothane-triggered-ca2-release-in-malignant-hyperthermia-susceptible-muscle
#16
Alberto Zullo, Martin Textor, Philipp Elischer, Stefan Mall, Andreas Alt, Werner Klingler, Werner Melzer
Malignant hyperthermia (MH) is a fatal hypermetabolic state that may occur during general anesthesia in susceptible individuals. It is often caused by mutations in the ryanodine receptor RyR1 that favor drug-induced release of Ca2+ from the sarcoplasmic reticulum. Here, knowing that membrane depolarization triggers Ca2+ release in normal muscle function, we study the cross-influence of membrane potential and anesthetic drugs on Ca2+ release. We used short single muscle fibers of knock-in mice heterozygous for the RyR1 mutation Y524S combined with microfluorimetry to measure intracellular Ca2+ signals...
December 15, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29241198/fam3a-protects-against-glutamate-induced-toxicity-by-preserving-calcium-homeostasis-in-differentiated-pc12-cells
#17
Qing Song, Wen-Li Gou, Yu-Liang Zou
BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29237755/differential-contribution-of-ca2-sources-to-day-and-night-bk-current-activation-in-the-circadian-clock
#18
Joshua P Whitt, Beth A McNally, Andrea L Meredith
Large conductance K+ (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca2+ (Ca2+i). To enable this regulation, BK channels functionally couple to both voltage-gated Ca2+ channels (VGCCs) and channels mediating Ca2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca2+i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca2+i are reduced...
December 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29235708/chlorantraniliprole-resistance-and-its-biochemical-and-new-molecular-target-mechanisms-in-laboratory-and-field-strains-of-chilo-suppressalis-walker
#19
Sun Yang, Lu Xu, Chen Qiong, Wenjing Qin, Huang Shuijin, Houguo Qin
BACKGROUND: The rice striped stem borer (SSB), Chilo suppressalis (Walker), is one of the most economically important and destructive rice pests in China. To date, the efficiency of conventional insecticides has decreased greatly because of the development of high resistance. Since the introduction of chlorantraniliprole in 2008, SSB has presented resistance issues. RESULTS: In this study, lab resistant strains R1 and R2 (RR of 38.8 and 110.4, respectively) were established and a field population HR (RR of 249...
December 13, 2017: Pest Management Science
https://www.readbyqxmd.com/read/29235522/an-optogenetic-arrhythmia-model-to-study-catecholaminergic-polymorphic-ventricular-tachycardia-mutations
#20
Elisabeth Fischer, Alexander Gottschalk, Christina Schüler
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition of abnormal heart rhythm (arrhythmia), induced by physical activity or stress. Mutations in ryanodine receptor 2 (RyR2), a Ca2+ release channel located in the sarcoplasmic reticulum (SR), or calsequestrin 2 (CASQ2), a SR Ca2+ binding protein, are linked to CPVT. For specific drug development and to study distinct arrhythmias, simple models are required to implement and analyze such mutations. Here, we introduced CPVT inducing mutations into the pharynx of Caenorhabditis elegans, which we previously established as an optogenetically paced heart model...
December 13, 2017: Scientific Reports
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