Rate-dependent prolongation of action potential duration in single ventricular myocytes obtained from hearts of rats with streptozotocin-induced chronic diabetes sustained for 30-32 weeks.

We examined the characteristics of the action potentials of single ventricular myocytes obtained from the hearts of rats with chronically-induced diabetes. Male Wistar rats were made diabetic by injecting streptozotocin (65 mg/kg) and 30-32 weeks later the hearts were excised and used for an electrophysiological study. Action potentials were recorded from isolated right ventricular myocytes by an electrode fabricated for patch clamp in the whole-cell recording configuration. The action potential durations (APDs) of steady state chronic diabetic rat myocytes were longer than those of age-matched normal rat myocytes at all levels of repolarization (APD25, APD50, APD75, and APD90). As the stimulation frequency was increased (0.2-2 Hz), the APDs were lengthened in both diabetic and normal rats, and the difference of APDs between the groups was greater when the stimulation frequency was higher. When we examined alterations of APDs under conditions of train stimulation (2Hz, 20 stimuli), (1) the APDs in both groups were prolonged, and (2) the degree of prolongation of APD was significantly greater and the rate of APD prolongation was significantly faster in myocytes from the diabetic rats. The prolongation of APD in these heart cells is probably secondary to alteration of the transient outward current Ito, and sheds light on repolarization abnormality in cases of diabetic cardiomyopathy.