Orphaned ryanodine receptors in the failing heart

doi:10.1073/pnas.0509324103

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	Orphaned ryanodine receptors in the failing heart
	Song, LS ; Sobie, EA ; McCulle, S ; Lederer, WJ ; Balke, CW ; Cheng, HP
刊名	proceedings of the national academy of sciences of the united states of america
	2006
关键词	calcium signaling local control dyssynchrony heart failure transverse tubules SARCOPLASMIC-RETICULUM CA2+ RAT VENTRICULAR MYOCYTES ACTION-POTENTIAL REPOLARIZATION CARDIAC MYOCYTES TRANSVERSE TUBULES CALCIUM TRANSIENTS T-TUBULES FAILURE RELEASE MUSCLE
DOI	10.1073/pnas.0509324103
英文摘要	Heart muscle is characterized by a regular array of proteins and structures that form a repeating functional unit identified as the sarcomere. This regular structure enables tight coupling between electrical activity and Ca2+ signaling. In heart failure, multiple cellular defects develop, including reduced contractility, altered Ca2+ signaling, and arrhythmias; however, the underlying causes of these defects are not well understood. Here, in ventricular myocytes from spontaneously hypertensive rats that develop heart failure, we identify fundamental changes in Ca2+ signaling that are related to restructuring of the spatial organization of the cells. Myocytes display both a reduced ability to trigger sarcoplasmic reticulum Ca2+ release and increased spatial dispersion of the transverse tubules (TTs). Remodeled TTs in cells from failing hearts no longer exist in the regularly organized structures found in normal heart cells, instead moving within the sarcomere away from the Vine structures and leaving behind the sarcoplasmic reticulum Ca2+ release channels, the ryanodine receptors (RyRs). These orphaned RyRs appear to be responsible for the dyssynchronous Ca2+ sparks that have been linked to blunted contractility and, probably, Ca2+-dependent arrhythmias in diverse models of heart failure. We conclude that the increased spatial dispersion of the TTs and orphaned RyRs lead to the loss of local control and Ca2+ instability in heart failure.; Multidisciplinary Sciences; SCI(E); 194; ARTICLE; 11; 4305-4310; 103
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/398718]
专题	生命科学学院
推荐引用方式 GB/T 7714	Song, LS,Sobie, EA,McCulle, S,et al. Orphaned ryanodine receptors in the failing heart[J]. proceedings of the national academy of sciences of the united states of america,2006.
APA	Song, LS,Sobie, EA,McCulle, S,Lederer, WJ,Balke, CW,&Cheng, HP.(2006).Orphaned ryanodine receptors in the failing heart.proceedings of the national academy of sciences of the united states of america.
MLA	Song, LS,et al."Orphaned ryanodine receptors in the failing heart".proceedings of the national academy of sciences of the united states of america (2006).