Streptozotocin-induced diabetes in rats prolonged action potential duration and reduced the amplitude and slowed reactivation of the transient outward K+ current compared to controls.
Does STZ-induced diabetes alter action potential duration and outward K+ currents in rat ventricular myocytes?
Short-term STZ-induced diabetes in rats prolongs ventricular action potential duration and attenuates outward K+ currents, effects that are independent of hypothyroidism and preventable by blocking hyperglycemia.
The electrophysiological properties of single ventricular myocytes from control rats and from rats made diabetic by streptozotocin (STZ) injection (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 myocytes from diabetic rats. In ventricular myocytes from diabetic rats, the Ca(2+)-independent transient outward K+ current (I(t)) is reduced in amplitude, and its reactivation kinetics are slowed. These changes result in a smaller I(t) at physiological heart rates. The steady-state outward K+ current (IK) also exhibits rate-dependent attenuation, and this phenomenon is more pronounced in cells from diabetic rats. These STZ-induced changes in I(t) and IK 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 hypothyroid conditions that accompany the diabetic state, since they cannot be reversed by replacement of the hormone L-triiodothyronine to physiological levels. Direct effects of STZ could be ruled out, since preceding the STZ injection with a bolus injection of 3-O-methylglucose, which prevents development of hyperglycemia, prevents the electrophysiological changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimoni et al. (Fri,) conducted a other in Diabetes. Streptozotocin vs. Control was evaluated on Action potential duration and outward K+ currents. Streptozotocin-induced diabetes in rats prolonged action potential duration and reduced the amplitude and slowed reactivation of the transient outward K+ current compared to controls.