Elevated sarcoplasmic reticulum Ca2+ leak in intact ventricular myocytes from rabbits in heart failure

Thomas R. Shannon, Steven M. Pogwizd, Donald M Bers

Research output: Contribution to journalArticle

260 Scopus citations

Abstract

Altered sarcoplasmic reticulum (SR) Ca2+-ATPase and Na +-Ca2+ exchange (NCX) function have been implicated in depressing SR Ca2+ content and contractile function in heart failure (HF). Enhanced diastolic ryanodine receptor (RyR) leak could also lower SR Ca2+ load in HF, but direct cellular measurements are lacking. In this study, we measure SR Ca2+ leak directly in intact isolated rabbit ventricular myocytes from a well-developed nonischemic HF model. Abrupt block of SR Ca2+ leak by tetracaine shifts Ca2+ from the cytosol to SR. The tetracaine-induced decline in [Ca2+]i and increase total SR Ca2+ load ([Ca2+]SRT) directly indicate the SR Ca2+ leak (before tetracaine). Diastolic SR Ca2+ leak increases with [Ca2+]SRT, and for any [Ca2+]SRT is greater in HF versus control. Mathematical modeling was used to compare the relative impact of alterations in SR Ca2+ leak, SR Ca2+-ATPase, and Na+-Ca 2+ exchange on SR Ca2+ load in HF. We conclude that increased diastolic SR Ca2+ leak in HF may contribute to reductions in SR Ca2+ content, but changes in NCX in this HF model have more impact on [Ca2+]SRT.

Original languageEnglish (US)
Pages (from-to)592-594
Number of pages3
JournalCirculation Research
Volume93
Issue number7
DOIs
StatePublished - Oct 3 2003
Externally publishedYes

Keywords

  • Ca pump
  • Excitation-contraction coupling
  • Heart failure
  • Ryanodine receptors
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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