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 language | English (US) |
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Pages (from-to) | 592-594 |
Number of pages | 3 |
Journal | Circulation Research |
Volume | 93 |
Issue number | 7 |
DOIs | |
State | Published - Oct 3 2003 |
Externally published | Yes |
Keywords
- Ca pump
- Excitation-contraction coupling
- Heart failure
- Ryanodine receptors
- Sarcoplasmic reticulum
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine