Ultrastructural remodelling of Ca2+ signalling apparatus in failing   heart cells

doi:10.1093/cvr/cvs195

CORC > 北京大学 > 生命科学学院

	Ultrastructural remodelling of Ca2+ signalling apparatus in failing heart cells
	Wu, Hao-Di ; Xu, Ming ; Li, Rong-Chang ; Guo, Liang ; Lai, Ying-Si ; Xu, Shi-Ming ; Li, Su-Fang ; Lu, Quan-Long ; Li, Lin-Lin ; Zhang, Hai-Bo ; Zhang, You-Yi ; Zhang, Chuan-Mao ; Wang, Shi-Qiang
刊名	cardiovascular research
	2012
关键词	Heart failure Ultrastructure Calcium channel Excitationcontraction coupling RYANODINE RECEPTORS SARCOPLASMIC-RETICULUM VENTRICULAR MYOCYTES CARDIAC MYOCYTES T-TUBULES DIHYDROPYRIDINE RECEPTORS SKELETAL-MUSCLE CALCIUM-RELEASE FAILURE HYPERTROPHY
DOI	10.1093/cvr/cvs195
英文摘要	The contraction of a heart cell is controlled by Ca-2-induced Ca-2 release between L-type Ca-2 channels (LCCs) in the cell membrane/T-tubules (TTs) and ryanodine receptors (RyRs) in the junctional sarcoplasmic reticulum (SR). During heart failure, LCCRyR signalling becomes defective. The purpose of the present study was to reveal the ultrastructural mechanism underlying the defective LCCRyR signalling and contractility. In rat models of heart failure produced by transverse aortic constriction surgery, stereological analysis of transmission electron microscopic images showed that the volume density and the surface area of junctional SRs and those of SR-coupled TTs were both decreased in failing heart cells. The TTSR junctions were displaced or missing from the Z-line areas. Moreover, the spatial span of individual TTSR junctions was markedly reduced in failing heart cells. Numerical simulation and junctophilin-2 knockdown experiments demonstrated that the decrease in junction size (and thereby the constitutive LCC and RyR numbers) led to a scattered delay of Ca-2 release activation. The shrinking and eventual absence of TTSR junctions are important mechanisms underlying the desynchronized and inhomogeneous Ca-2 release and the decreased contractile strength in heart failure. Maintaining the nanoscopic integrity of TTSR junctions thus represents a therapeutic strategy against heart failure and related cardiomyopathies.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000307781800008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Cardiac & Cardiovascular Systems; SCI(E); 32; ARTICLE; 4; 430-438; 95
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/320206]
专题	生命科学学院
推荐引用方式 GB/T 7714	Wu, Hao-Di,Xu, Ming,Li, Rong-Chang,et al. Ultrastructural remodelling of Ca2+ signalling apparatus in failing heart cells[J]. cardiovascular research,2012.
APA	Wu, Hao-Di.,Xu, Ming.,Li, Rong-Chang.,Guo, Liang.,Lai, Ying-Si.,...&Wang, Shi-Qiang.(2012).Ultrastructural remodelling of Ca2+ signalling apparatus in failing heart cells.cardiovascular research.
MLA	Wu, Hao-Di,et al."Ultrastructural remodelling of Ca2+ signalling apparatus in failing heart cells".cardiovascular research (2012).