CAS OpenIR  > 中科院上海应用物理研究所2004-2010年
Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia
Liang, X; Chen, KY; Fruen, B; Hu, J(胡钧); Ma, JJ; Hu, XF; Parness, J; Liang, X (reprint author), Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, 800 Dong Chuan Rd, Shanghai 200240, Peoples R China
2009
Source PublicationINTEGRATIVE BIOLOGY
ISSN1757-9694
Volume1Issue:40764Pages:533
AbstractFunctional coupling between clustered membrane receptors has been identified as a novel mechanism to improve signaling performance in a number of physiological processes. The potential role of defective inter-receptor coupling in the pathogenesis of disease, however, has not previously been explored. Ryanodine receptors (RyRs), the primary calcium release channel of muscle, usually form ordered two-dimensional arrays in the sarcoplasmic reticulum membranes. Mutations in RyRs are known to cause a number of severe diseases both in skeletal muscle and in heart. Here we present a model demonstrating how impaired functional coupling between neighboring mutant RyR1(R615C) channels may contribute to the pharmacogenetic skeletal muscle sensitivity, malignant hyperthermia (MH). We find that purified RyR1(R615C) from MH susceptible porcine skeletal muscle shows significantly reduced oligomerization when compared to RyR1(WT), indicating a potential loss of intrinsic intermolecular control. The MH-triggering volatile anesthetic, halothane, activates RyR1(R615C) and RyR1WT to a similar extent, using [(3)H] ryanodine binding as a measure of activation. Modeling RyR1 array function with parameters modified to simulate the loss of functional inter-RyR coupling recapitulates the MH molecular phenotype-RyR1 channels leaky to Ca(2+) at rest and long open-times following exposure to halothane. Our work suggests that a defect in inter-RyR1 coupling is a novel direction for research into the pathogenesis of MH.
Subject AreaCell Biology
Indexed BySCI
Language英语
Funding Project应物所项目组
WOS IDWOS:000269681600005
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/7750
Collection中科院上海应用物理研究所2004-2010年
Corresponding AuthorLiang, X (reprint author), Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, 800 Dong Chuan Rd, Shanghai 200240, Peoples R China
Recommended Citation
GB/T 7714
Liang, X,Chen, KY,Fruen, B,et al. Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia[J]. INTEGRATIVE BIOLOGY,2009,1(40764):533.
APA Liang, X.,Chen, KY.,Fruen, B.,Hu, J.,Ma, JJ.,...&Liang, X .(2009).Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia.INTEGRATIVE BIOLOGY,1(40764),533.
MLA Liang, X,et al."Impaired interaction between skeletal ryanodine receptors in malignant hyperthermia".INTEGRATIVE BIOLOGY 1.40764(2009):533.
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