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The cardiac ryanodine receptor luminal Ca2+ sensor governs Ca2+ waves, ventricular tachyarrhythmias and cardiac hypertrophy in calsequestrin-null mice

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资源类型：
作者：
Zhang, J[a,d] * ; Chen, B[b] ; Zhong, X[c] ; Mi, T[c,e] ; Guo, A[b] ; Zhou, Q[a,d] ; Tan, Z[a] ; Wu, G[a] ; Chen, A.W[c] ; Fill, M[a] ; Song, L.-S[b] ; Chen, S.R.W[a,c] ;
单位： [a]Rush University Medical Center, 1750 West Harrison Street, 1229 JS, Chicago, IL 60612, United States [b]Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, United States [c]Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada [d]Department of Cardiology of Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China [e]Department of Geriatrics of Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China
出处：
DOI： 10.1042/BJ20140126
ISSN：

关键词： Calsequestrin Cardiomyopathy Ryanodine receptor Sarcoplasmic reticulum

摘要：
CASQ2 (cardiac calsequestrin) is commonly believed to serve as the SR (sarcoplasmic reticulum) luminal Ca2+ sensor. Ablation of CASQ2 promotes SCWs (spontaneous Ca2+ waves) and CPVT (catecholaminergic polymorphic ventricular tachycardia) upon stress but not at rest. How SCWs and CPVT are triggered by stress in the absence of the CASQ2-based luminal Ca 2+ sensor is an important unresolved question. In the present study, we assessed the role of the newly identified RyR2 (ryanodine receptor 2)-resident luminal Ca2+ sensor in determining SCW propensity, CPVT susceptibility and cardiac hypertrophy in Casq2-KO (knockout) mice. We crossbred Casq2-KO mice with RyR2 mutant (E4872Q+/-) mice, which lack RyR2-resident SR luminal Ca2+ sensing, to generate animals with both deficiencies. Casq2+/- and Casq2-/- mice showed stress-induced VTs (ventricular tachyarrhythmias), whereas Casq2 +/-/E4872Q+/- and Casq2-/-/E4872Q+/- mice displayed little or no stress-induced VTs. Confocal Ca2+ imaging revealed that Casq2-/- hearts frequently exhibited SCWs after extracellular Ca2+ elevation or adrenergic stimulation, whereas Casq2-/-/E4872Q+/- hearts had few or no SCWs under the same conditions. Cardiac hypertrophy developed and CPVT susceptibility increased with age in Casq2-/- mice, but not in Casq2-/-/ E4872Q+/- mice. However, the amplitudes and dynamics of voltage-induced Ca2+ transients in Casq2-/- and Casq2 -/-/E4872Q+/- hearts were not significantly different. Our results indicate that SCWs, CPVT and hypertrophy in Casq2-null cardiac muscle are governed by the RyR2-resident luminal Ca2+ sensor. This implies that defects in CASQ2-based luminal Ca2+ sensing can be overridden by the RyR2-resident luminal Ca2+ sensor. This makes this RyR2-resident sensor a promising molecular target for the treatment of Ca2+- mediated arrhythmias. © The Authors Journal compilation © 2014 Biochemical Society.

语种：
外文
中科院(CAS)分区：
出版当年[2013]版：
大类 | 2 区 生物
小类 | 3 区 生化与分子生物学
最新[2025]版：
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学
第一作者：
第一作者单位： [a]Rush University Medical Center, 1750 West Harrison Street, 1229 JS, Chicago, IL 60612, United States [d]Department of Cardiology of Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China
通讯作者：
通讯机构： [a]Rush University Medical Center, 1750 West Harrison Street, 1229 JS, Chicago, IL 60612, United States [c]Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada
推荐引用方式(GB/T 7714)：
Zhang J,Chen B,Zhong X,et al.The cardiac ryanodine receptor luminal Ca2+ sensor governs Ca2+ waves, ventricular tachyarrhythmias and cardiac hypertrophy in calsequestrin-null mice[J].Biochemical Journal.2014,461(1):doi:10.1042/BJ20140126.
APA：
Zhang, J,Chen, B,Zhong, X,Mi, T,Guo, A...&Chen, S.R.W.(2014).The cardiac ryanodine receptor luminal Ca2+ sensor governs Ca2+ waves, ventricular tachyarrhythmias and cardiac hypertrophy in calsequestrin-null mice.Biochemical Journal,461,(1)
MLA：
Zhang, J,et al."The cardiac ryanodine receptor luminal Ca2+ sensor governs Ca2+ waves, ventricular tachyarrhythmias and cardiac hypertrophy in calsequestrin-null mice".Biochemical Journal 461..1(2014)

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