Role of the sarcoplasmic reticulum in altered action potential and contraction of myopathic human and hamster ventricle.

1. The present experiments were performed in order to study the role of the sarcoplasmic reticulum (SR) in the altered action potential and contraction of ventricular myocardium obtained from myopathic Syrian hamster and explanted human hearts (n = 8). The hamsters included age-matched healthy hamsters (F1B; n = 18), young myopathic hamsters (Bio 14.6; n = 8; aged 17-27 weeks) and older myopathic hamsters (n = 10; aged 39-43 weeks). 2. Action potentials were recorded by means of a microelectrode technique and force was recorded using a transducer. Post-rest potentiation of contraction (PRPC), a measure of the SR Ca2+-pumping activity, was determined after different rest intervals (2-60 s). Furthermore, cyclopiazonic acid (10 micro mol/L), a specific blocker of SR Ca2+-ATPase, was used to unmask abnormalities in the function of the SR. 3. The relationship between PRPC and rest interval was similar in younger healthy and myopathic hamsters, but the curve of the older myopathic muscle was obviously shifted downwards. Cyclopiazonic acid decreased predominantly the ascending part of the curve in both the healthy and myopathic hamster myocardium and could induce spontaneous action potentials during drug exposure or after washout. 4. In human myopathic myocardium, the curve of the PRPC-rest interval peaked at longer intervals (40-60 s) compared with that of the hamsters (10-20 s). Cyclopiazonic acid markedly depressed the relationship and increased the diastolic force (contracture) at high driving frequency, but did not induce action potentials during the rest interval. 5. We conclude that an impaired function of the SR contributes to the progressive deterioration of ventricular function in dilated cardiomyopathy and that the electromechanical behaviour of the ventricular myocardium of patients affected by dilated cardiomyopathy shows similarity and differences with the myopathic Syrian hamster model.