Two components of transient outward current in canine ventricular myocytes

Abstract

Repolarization during phase 1 of cardiac action potential is important in that it may influence both impulse conduction in partially depolarized tissue and action potential duration. Thus, it is important to know the properties and regulation of the underlying currents. In about 50% of canine ventricular myocytes, the action potential displays a phase 1 of fast repolarization and a prominent notch between phase 1 and the plateau. A transient outward current is responsible for both. This current is composed of two components: one (I(to1)) blocked by 4-aminopyridine and the other (I(to2)) blocked by manganese. In the present study, we characterized each of the components in isolation from the other. Both had an activation threshold between -30 and -20 mV. At the same voltage, I(to1) was larger than I(to2) and had a shorter time to peak. The peak current-voltage relationship for I(to1) was almost linear, but that for I(to2) was bell-shaped. I(to1) decayed during sustained depolarization with a single exponential time course: τ < 30 msec at all voltages. It recovered from inactivation with a voltage-dependent time course: τ = 70 msec at -90 mV and 720 msec at -40 mV. I(to2) was augmented by elevating [Ca2+](o) or by isoproterenol. It was inhibited by caffeine, ryanodine, or a preceding transient inward current, suggesting that it was activated by intracellular calcium released from sarcoplasmic reticulum. We conclude that I(to1) and I(to2) in canine ventricle are similar to those described for many other cardiac tissues, but the kinetics of I(to1) are significantly faster than in other tissues.