ABNORMALITIES K+ AND CA2+ CURRENTS IN VENTRICULAR MYOCYTES FROM RATS WITH CHRONIC DIABETES

Ionic mechanisms related to the prolongation of cardiac action potenti al in rats with chronic diabetes mellitus were studied using whole cel l voltage-clamp techniques. Diabetes was induced by injection of strep tozotocin (STZ; 65 mg/kg body wt) into the tail vein, and ventricular myocytes were isolated from STZ-injected rats (24-30 wk) and from age- matched normal rats. The current densities of transient outward curren t (I-to), a steady-state outward current, and L-type Ca2+ current (I-C a) were significantly smaller in cells from diabetic animals. In addit ion, the kinetics of I-to of diabetic cells were modified. 1) The deca y of I-to was well fitted by a sum of two exponential components in no rmal cells; there was only one (slow) component in the diabetic cells. 2) The steady-state inactivation curve of I-to in diabetic cells shif ted by 5 mV in the negative direction. 3) Recovery from inactivation o f I-to was slower in cells from diabetic animals. These alterations in I-to and the steady-state outward current can account for most of the action potential prolongation heretofore documented. The decrease of I-Ca may possibly be related to the depressed contraction seen in chro nic diabetic mellitus.