SHORT-TERM DIABETES ALTERS K+ CURRENTS IN RAT VENTRICULAR MYOCYTES

The electrophysiological properties of single ventricular myocytes fro m control rats and from rats made diabetic by streptozotocin (STZ) inj ection (100 mg/kg body weight) have been investigated using whole-cell voltage-clamp measurements. Our major goal was to define the effects of diabetes on rate-dependent changes in action potential duration and the underlying outward K+ currents. As early as 4 to 6 days after STZ treatment, significant elevation of plasma glucose levels occurs, and the action potential duration increases. In both control and diabetic rats, when the stimulation rate is increased, the action potential is prolonged, but this lengthening is considerably more pronounced in my ocytes from diabetic rats. In ventricular myocytes from diabetic rats, the Ca2+-independent transient outward K+ current (I(t)) is reduced i n amplitude, and its reactivation kinetics are slowed. These changes r esult in a smaller I(t) at physiological heart rates. The steady-state outward K+ current (I(K)) also exhibits rate-dependent attenuation, a nd this phenomenon is more pronounced in cells from diabetic rats. The se STZ-induced changes in I(t) and I(K) also develop when a lower dose (55 mg/kg) of STZ is used and measurements are made after 7 weeks of treatment. These electrophysiological effects are not related to the h ypothyroid conditions that accompany the diabetic state, since they ca nnot be reversed by replacement of the hormone L-triiodothyronine to p hysiological levels. Direct effects of STZ could be ruled out, since p receding the STZ injection with a bolus injection of 3-O-methylglucose , which prevents development of hyperglycemia, prevents the electrophy siological changes. These results provide new insights into the ionic mechanism(s) involved in cardiovascular complications of diabetes, and they have implications for the metabolic regulation of K+ channel kin etics.