A RAPIDLY ACTIVATING SUSTAINED K-CONTRACTION COUPLING IN ADULT-MOUSE VENTRICLE( CURRENT MODULATES REPOLARIZATION AND EXCITATION)

1. The K+ currents which control repolarization in adult mouse ventric le, and the effects of changes in action potential duration on excitat ion-contraction coupling in this tissue, have been studied with electr ophysiological methods using single cell preparations and by recording mechanical parameters from an in vitro working heart preparation. 2. Under conditions where Ca2+-dependent currents were eliminated by buff ering intracellular Ca2+ with EGTA, depolarizing voltage steps elicite d two rapidly activating outward K+ currents: (i) a transient outward current, and (ii) a slowly inactivating or 'sustained' delayed rectifi er. 3. These two currents were separated pharmacologically by the K+ c hannel blocker 4-aminopyridine (4-AP). 4-AP at concentrations between 3 and 200 mu M resulted in (i) a marked increase in action potential d uration and a large decrease in the sustained K+ current at plateau po tentials, as well as (ii) a significant increase in left ventricular s ystolic pressure in the working heart preparation. 4. The current-volt age (I-V) relation, kinetics, and block by low concentrations of 4-AP strongly suggest that the rapid delayed rectifier in adult mouse ventr icle is the same K+ current (Kv1.5) that has been characterized in det ail in human and canine atria. 5. These results show that the 4-AP-sen sitive rapid delayed rectifier is a very important repolarizing curren t in mouse ventricle. The enhanced contractility produced by 4-AP (50 mu M) in the working: heart preparation demonstrates that modulation o f the action potential duration, by blocking a K+ current, is a very s ignificant inotropic variable.