Role of voltage-sensitive release mechanism in depression of cardiac contraction in myopathic hamsters

We investigated excitation-contraction (EC) coupling in isolated ventricula r myocytes from prehypertrophic cardiomyopathic (CM) hamster hearts. Conven tional and voltage-clamp recordings were made with high-resistance microele ctrodes, and cell shortening was measured with a video-edge detector at 37 degrees C. Contractions were depressed in myocytes from CM hearts, whether they were initiated by action potentials or voltage-clamp steps. As in guin ea pig and rat, contraction in hamster myocytes could be triggered by a vol tage-sensitive release mechanism (VSRM) or Ca2+-induced Ca2+ release (CICR) . Selective activation of these mechanisms demonstrated that the defect in EC coupling was primarily caused by a defect in the VSRM. However, activati on and inactivation properties of the VSRM were not altered. When the VSRM was inhibited, the remaining contractions induced by CICR exhibited identic al bell-shaped contraction voltage relations in normal and CM myocytes. Inw ard Ca2+ current was unchanged. Thus a defect in the VSRM component of EC c oupling precedes the development of hypertrophy and failure in CM hamster h eart.