Ultrastructural remodelling of Ca2+ signalling apparatus in failing heart cells

被引：71

作者：

Wu, Hao-Di ^{[1
,2
]}

Xu, Ming ^{[1
,2
]}

Li, Rong-Chang ^{[1
,2
]}

Guo, Liang ^{[1
,2
]}

Lai, Ying-Si ^{[1
,2
]}

Xu, Shi-Ming ^{[1
,2
]}

Li, Su-Fang ^{[1
,2
]}

Lu, Quan-Long ^{[1
,2
]}

Li, Lin-Lin ^{[1
,2
]}

Zhang, Hai-Bo ^{[3
]}

Zhang, You-Yi ^{[1
,2
]}

Zhang, Chuan-Mao ^{[1
,2
]}

Wang, Shi-Qiang ^{[1
,2
]}

机构：

[1] Peking Univ, State Key Lab Biomembrane & Membrane Biotechnol, Key Lab Cell Proliferat & Differentiat,Hosp 3, Key Lab Mol Cardiovasc Sci,Key Lab Cardiovasc Mol, Beijing, Peoples R China

[2] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China

[3] Capital Med Univ, Anzhen Hosp, Beijing, Peoples R China

来源：

CARDIOVASCULAR RESEARCH | 2012年 / 95卷 / 04期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

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;

D O I：

10.1093/cvr/cvs195

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

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.

引用

页码：430 / 438

页数：9

共 43 条

[1] STEREOLOGICAL MEASUREMENT OF CELLULAR AND SUBCELLULAR HYPERTROPHY AND HYPERPLASIA IN THE PAPILLARY-MUSCLE OF ADULT-RAT [J].