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Defects in T-tubular electrical activity underlie local alterations of calcium release in heart failure.

ABSTRACT: Action potentials (APs), via the transverse axial tubular system (TATS), synchronously trigger uniform Ca(2+) release throughout the cardiomyocyte. In heart failure (HF), TATS structural remodeling occurs, leading to asynchronous Ca(2+) release across the myocyte and contributing to contractile dysfunction. In cardiomyocytes from failing rat hearts, we previously documented the presence of TATS elements which failed to propagate AP and displayed spontaneous electrical activity; the consequence for Ca(2+) release remained, however, unsolved. Here, we develop an imaging method to simultaneously assess TATS electrical activity and local Ca(2+) release. In HF cardiomyocytes, sites where T-tubules fail to conduct AP show a slower and reduced local Ca(2+) transient compared with regions with electrically coupled elements. It is concluded that TATS electrical remodeling is a major determinant of altered kinetics, amplitude, and homogeneity of Ca(2+) release in HF. Moreover, spontaneous depolarization events occurring in failing T-tubules can trigger local Ca(2+) release, resulting in Ca(2+) sparks. The occurrence of tubule-driven depolarizations and Ca(2+) sparks may contribute to the arrhythmic burden in heart failure.

SUBMITTER: Crocini C

PROVIDER: S-EPMC4210349 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Defects in T-tubular electrical activity underlie local alterations of calcium release in heart failure.

Crocini Claudia C Coppini Raffaele R Ferrantini Cecilia C Yan Ping P Loew Leslie M LM Tesi Chiara C Cerbai Elisabetta E Poggesi Corrado C Pavone Francesco S FS Sacconi Leonardo L

Proceedings of the National Academy of Sciences of the United States of America 20141006 42

Action potentials (APs), via the transverse axial tubular system (TATS), synchronously trigger uniform Ca(2+) release throughout the cardiomyocyte. In heart failure (HF), TATS structural remodeling occurs, leading to asynchronous Ca(2+) release across the myocyte and contributing to contractile dysfunction. In cardiomyocytes from failing rat hearts, we previously documented the presence of TATS elements which failed to propagate AP and displayed spontaneous electrical activity; the consequence f ...[more]

PMID: 25288764

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Defects in T-tubular electrical activity underlie local alterations of calcium release in heart failure.

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Defects in T-tubular electrical activity underlie local alterations of calcium release in heart failure.

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