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Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells.

ABSTRACT: 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, LCC-RyR signalling becomes defective. The purpose of the present study was to reveal the ultrastructural mechanism underlying the defective LCC-RyR 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 TT-SR junctions were displaced or missing from the Z-line areas. Moreover, the spatial span of individual TT-SR 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 TT-SR 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 TT-SR junctions thus represents a therapeutic strategy against heart failure and related cardiomyopathies.

SUBMITTER: Wu HD

PROVIDER: S-EPMC3422078 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells.

Wu Hao-Di HD Xu Ming M Li Rong-Chang RC Guo Liang L Lai Ying-Si YS Xu Shi-Ming SM Li Su-Fang SF Lü Quan-Long QL Li Lin-Lin LL Zhang Hai-Bo HB Zhang You-Yi YY Zhang Chuan-Mao CM Wang Shi-Qiang SQ

Cardiovascular research 20120615 4

<h4>Aims</h4>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, LCC-RyR signalling becomes defective. The purpose of the present study was to reveal the ultrastructural mechanism underlying the defective LCC-RyR signalling and contractility.<h4>Methods and results</h4>In rat models of heart failu ...[more]

PMID: 22707157

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Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells.

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Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells.

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