Defective Excitation-Contraction Coupling in Experimental Cardiac Hypertrophy and Heart Failure

TLDR

The study examined excitation‑contraction coupling in single myocytes from hypertensive and heart‑failure rats using confocal microscopy and patch‑clamp, finding that the ability of the plasma‑membrane calcium current to trigger sarcoplasmic‑reticulum calcium release was diminished. The calcium‑current–driven release from the sarcoplasmic reticulum was impaired due to altered coupling between calcium channels, a defect that β‑adrenergic stimulation could largely rescue in hypertrophic but not failing cells, suggesting it contributes to heart failure when compensatory mechanisms fail.

Abstract

Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes taken from hypertensive rats (Dahl SS/Jr) and SH-HF rats in heart failure. Confocal microscopy and patch-clamp methods were used to examine excitation-contraction (EC) coupling, and the relation between the plasma membrane calcium current ( I Ca ) and evoked calcium release from the sarcoplasmic reticulum (SR), which was visualized as “calcium sparks.” The ability of I Ca to trigger calcium release from the SR in both hypertrophied and failing hearts was reduced. Because I Ca density and SR calcium-release channels were normal, the defect appears to reside in a change in the relation between SR calcium-release channels and sarcolemmal calcium channels. β-Adrenergic stimulation largely overcame the defect in hypertrophic but not failing heart cells. Thus, the same defect in EC coupling that develops during hypertrophy may contribute to heart failure when compensatory mechanisms fail.