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Elevated sarcoplasmic reticulum Ca$^2+$ leak in intact ventricular myocytes from rabbits in heart failure.

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Circ. Res., 93 (7): 592--594 (октября 2003)
DOI: 10.1161/01.RES.0000093399.11734.B3

Аннотация

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

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