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Ryanodine receptor type 2 heart

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https://www.readbyqxmd.com/read/29593014/ryanodine-receptor-calcium-leak-in-circulating-b-lymphocytes-as-a-biomarker-in-heart-failure
#1
Alexander Kushnir, Gaetano Santulli, Steven R Reiken, Ellie Coromilas, Sarah J Godfrey, Danielle L Brunjes, Paolo C Colombo, Melana Yuzefpolskaya, Seth I Sokol, Richard N Kitsis, Andrew R Marks
Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2+ is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2+ release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2+ leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2+ leak, contributing to myopathy and weakness...
March 28, 2018: Circulation
https://www.readbyqxmd.com/read/29521549/cardiac-adenovirus-associated-viral-presenilin-1-gene-delivery-protects-the-left-ventricular-function-of-the-heart-via-regulating-ryr2-function-in-post-ischaemic-heart-failure
#2
Tian Li, Yafeng Shen, Li Su, Xiaoyan Fan, Fangxing Lin, Xuting Ye, Dianer Ding, Ying Tang, Yongji Yang, Changhai Lei, Shi Hu
Post-ischaemic heart failure is a major cause of death worldwide. Reperfusion of infarcted heart tissue after myocardial infarction has been an important medical intervention to improve outcomes. However, disturbances in Ca2+ and redox homeostasis at the cellular level caused by ischaemia/reperfusion remain major clinical challenges. In this study, we investigated the potential of adeno-associated virus (AAV)-9-mediated cardiac expression of a Type-2 ryanodine receptor (RyR2) degradation-associated gene, Presenilin 1 (PSEN1), to combat post-ischaemic heart failure...
March 21, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29452352/conditional-ablation-and-conditional-rescue-models-for-casq2-elucidate-the-role-of-development-and-of-cell-type-specific-expression-of-casq2-in-the-cpvt2-phenotype
#3
Daniel J Flores, ThuyVy Duong, Luke O Brandenberger, Apratim Mitra, Aditya Shirali, John C Johnson, Danielle Springer, Audrey Noguchi, Zu-Xi Yu, Steven N Ebert, Andreas Ludwig, Bjorn C Knollmann, Mark D Levin, Karl Pfeifer
Cardiac calsequestrin (Casq2) associates with the ryanodine receptor 2 channel in the junctional sarcoplasmic reticulum to regulate Ca2+ release into the cytoplasm. Patients carrying mutations in CASQ2 display low resting heart rates under basal conditions and stress-induced polymorphic ventricular tachycardia (CPVT). In this study, we generate and characterize novel conditional deletion and conditional rescue mouse models to test the influence of developmental programs on the heart rate and CPVT phenotypes...
May 1, 2018: Human Molecular Genetics
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
#4
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/29248564/el20-a-potent-antiarrhythmic-compound-selectively-inhibits-calmodulin-deficient-ryanodine-receptor-type-2
#5
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 calcium cation (Ca2+ ) leak from the sarcoplasmic reticulum (SR). Calmodulin (CaM) dissociation from RyR2 has been associated with diastolic Ca2+ leak in heart failure. OBJECTIVE: Determine whether the tetracaine-derivative compound EL20 inhibits abnormal Ca2+ release from RyR2 in a CPVT model and investigate the underlying mechanism of inhibition...
April 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29029787/early-testosterone-replacement-attenuates-intracellular-calcium-dyshomeostasis-in-the-heart-of-testosterone-deprived-male-rats
#6
Punate Weerateerangkul, Krekwit Shinlapawittayatorn, Siripong Palee, Nattayaporn Apaijai, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca(2+) regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca(2+) regulation. However, the temporal changes of Ca(2+) dyshomeostasis in testosterone-deprived conditions are unclear. Moreover, the effects of early vs. late testosterone replacement are unknown...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29027245/epac-induced-ryanodine-receptor-type-2-activation-inhibits-sodium-currents-in-atrial-and-ventricular-murine-cardiomyocytes
#7
Haseeb Valli, Shiraz Ahmad, Sujan Sriharan, Lydia D Dean, Andrew A Grace, Kamalan Jeevaratnam, Hugh R Matthews, Christopher L-H Huang
Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca2+ homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na+ current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na+ currents. Plots of peak current against depolarisation from resting potential gave pretreatment maximum atrial and ventricular currents of -20...
March 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28875959/downregulation-of-na-ca-2-exchanger-isoform-1-protects-isolated-hearts-by-sevoflurane-postconditioning-but-not-by-delayed-remote-ischemic-preconditioning-in-rats
#8
Yang Yu, Cheng-Hui Zhou, Yun-Tai Yao, Li-Huan Li
Background: Calcium regulatory proteins-L-type Ca2+ channels (LTCCs), ryanodine receptor 2 (RyR2), and Na+ /Ca2+ exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model...
September 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28842915/roles-of-impaired-intracellular-calcium-cycling-in-arrhythmogenicity-of-diabetic-mouse-model
#9
Chung-Chuan Chou, Chien-Te Ho, Hui-Ling Lee, Yen Chu, Tzung-Hai Yen, Ming-Shien Wen, Shien-Fong Lin, Cheng-Hung Lee, Po-Cheng Chang
BACKGROUND: Diabetes mellitus is associated an increased risk of ventricular arrhythmias (VAs), but the underlying electrophysiological mechanisms are not fully explored. This study was aimed to test whether dynamic factors and Cai handling play roles in arrhythmogenesis of a diabetic animal model. METHODS: We used 26 db/db type 2 diabetes mice and 28 control mice in this study. VA inducibility was evaluated in vivo under isoflurane general anesthesia. The intracellular Ca(2+) (Cai ) and membrane voltage (Vm ) signals of the Langendorff-perfused mouse hearts were simultaneously recorded using the optical mapping technique...
August 26, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28736243/from-insulin-synthesis-to-secretion-alternative-splicing-of-type-2-ryanodine-receptor-gene-is-essential-for-insulin-secretion-in-pancreatic-%C3%AE-cells
#10
REVIEW
Hiroshi Okamoto, Shin Takasawa, Yasuhiko Yamamoto
Increases in the intracellular Ca2+ concentration in pancreatic islets, resulting from the Ca2+ mobilization from the intracellular source through the ryanodine receptor, are essential for insulin secretion by glucose. Cyclic ADP-ribose, a potent Ca2+ mobilizing second messenger synthesized from NAD+ by CD38, regulates the opening of ryanodine receptor. A novel ryanodine receptor mRNA (the islet-type ryanodine receptor) was found to be generated from the type 2 ryanodine receptor gene by the alternative splicing of exons 4 and 75...
October 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28702845/regulation-of-cardiac-ca-2-and-ion-channels-by-shear-mechanotransduction
#11
REVIEW
Joon-Chul Kim, Min-Jeong Son, Jun Wang, Sun-Hee Woo
Cardiac contraction is controlled by a Ca(2+) signaling sequence that includes L-type Ca(2+) current-gated opening of Ca(2+) release channels (ryanodine receptors) in the sarcoplasmic reticulum (SR). Local Ca(2+) signaling in the atrium differs from that in the ventricle because atrial myocytes lack transverse tubules and have more abundant corbular SR. Myocardium is subjected to a variety of forces with each contraction, such as stretch, shear stress, and afterload, and adapts to those mechanical stresses...
July 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28636428/fk506-binding-proteins-12-and-12-6-fkbps-as-regulators-of-cardiac-ryanodine-receptors-insights-from-new-functional-and-structural-knowledge
#12
Luis A Gonano, Peter P Jones
Ryanodine Receptors (RyRs) are intracellular Ca(2+) channels that mediate Ca(2+) flux from the sarco(endo)plasmic reticulum in many cell types. The interaction of RyRs with FK506-binding proteins (FKBPs) has been proposed as an important regulatory mechanism, where the loss of this interaction leads to channel dysfunction. In the heart, phosphorylation of RyR has been suggested to disrupt the RyR-FKBP interaction promoting altered Ca(2+) signaling, heart failure and arrhythmias. However, the functional result of FKBP interaction with RyR and how this interaction is regulated remains highly controversial...
September 3, 2017: Channels
https://www.readbyqxmd.com/read/28630041/dysregulated-zn-2-homeostasis-impairs-cardiac-type-2-ryanodine-receptor-and-mitsugumin-23-functions-leading-to-sarcoplasmic-reticulum-ca-2-leakage
#13
COMPARATIVE STUDY
Benedict Reilly-O'Donnell, Gavin B Robertson, Angela Karumbi, Connor McIntyre, Wojciech Bal, Miyuki Nishi, Hiroshi Takeshima, Alan J Stewart, Samantha J Pitt
Aberrant Zn2+ homeostasis is associated with dysregulated intracellular Ca2+ release, resulting in chronic heart failure. In the failing heart a small population of cardiac ryanodine receptors (RyR2) displays sub-conductance-state gating leading to Ca2+ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca2+ leakage through an uncharacterized mechanism. We sought to examine the role of Zn2+ in shaping intracellular Ca2+ release in cardiac muscle...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28620067/allele-specific-silencing-of-mutant-mrna-rescues-ultrastructural-and-arrhythmic-phenotype-in-mice-carriers-of-the-r4496c-mutation-in-the-ryanodine-receptor-gene-ryr2
#14
Rossana Bongianino, Marco Denegri, Andrea Mazzanti, Francesco Lodola, Alessandra Vollero, Simona Boncompagni, Silvia Fasciano, Giulia Rizzo, Damiano Mangione, Serena Barbaro, Alessia Di Fonso, Carlo Napolitano, Alberto Auricchio, Feliciano Protasi, Silvia G Priori
RATIONALE: Mutations in the cardiac Ryanodine Receptor gene (RYR2) cause dominant catecholaminergic polymorphic ventricular tachycardia (CPVT), a leading cause of sudden death in apparently healthy individuals exposed to emotions or physical exercise. OBJECTIVE: We investigated the efficacy of allele-specific silencing by RNA interference to prevent CPVT phenotypic manifestations in our dominant CPVT mice model carriers of the heterozygous mutation R4496C in RYR2...
August 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28499500/ca-2-release-channels-join-the-resolution-revolution
#15
REVIEW
Ran Zalk, Andrew R Marks
Ryanodine receptors (RyRs) are calcium release channels expressed in the sarcoendoplasmic reticula of many cell types including cardiac and skeletal muscle cells. In recent years Ca2+ leak through RyRs has been implicated as a major contributor to the development of diseases including heart failure, muscle myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of multiple functional states have clarified longstanding questions including the architecture of the transmembrane (TM) pore and cytoplasmic domains, the location and architecture of the channel gate, ligand-binding sites, and the gating mechanism...
July 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28487342/calcium-calmodulin-dependent-protein-kinase-ii-activity-persists-during-chronic-%C3%AE-adrenoceptor-blockade-in-experimental-and-human-heart-failure
#16
Matthias Dewenter, Stefan Neef, Christiane Vettel, Simon Lämmle, Christina Beushausen, Laura C Zelarayan, Sylvia Katz, Albert von der Lieth, Stefanie Meyer-Roxlau, Silvio Weber, Thomas Wieland, Samuel Sossalla, Johannes Backs, Joan H Brown, Lars S Maier, Ali El-Armouche
BACKGROUND: Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF...
May 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28469494/studying-dyadic-structure-function-relationships-a-review-of-current-modeling-approaches-and-new-insights-into-ca-2-mis-handling
#17
Mary M Maleckar, Andrew G Edwards, William E Louch, Glenn T Lines
Excitation-contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation-contraction coupling in both normal and diseased cardiac myocytes...
2017: Clinical Medicine Insights. Cardiology
https://www.readbyqxmd.com/read/28316073/arrhythmic-effects-of-epac-mediated-ryanodine-receptor-activation-in-langendorff-perfused-murine-hearts-are-associated-with-reduced-conduction-velocity
#18
Mengye Li, Sandeep S Hothi, Samantha C Salvage, Kamalan Jeevaratnam, Andrew A Grace, Christopher L-H Huang
Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention...
June 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#19
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
April 2017: Peptides
https://www.readbyqxmd.com/read/28216082/semi-automated-program-for-analysis-of-local-ca-2-spark-release-with-application-for-classification-of-heart-cell-type
#20
Moran Davoodi, Sofia Segal, Noa Kirschner Peretz, David Kamoun, Yael Yaniv
Local Ca2+ spark releases are essential to the Ca2+ cycling process. Thus, they play an important role in ventricular and atrial cell contraction, as well as in sinoatrial cell automaticity. Characterizing their properties in healthy cells from different regions in the heart can reveal the basic biophysical differences among these regions. We designed a semi-automatic Matlab Graphical User Interface (called Sparkalyzer) to characterize parameters of Ca2+ spark release from any major cardiac tissue, as recorded in line-scan mode with a confocal laser-scanning microscope...
June 2017: Cell Calcium
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