MEXILETINE-INDUCED SHORTENING OF THE ACTION-POTENTIAL DURATION OF VENTRICULAR MUSCLES BY ACTIVATION OF ATP-SENSITIVE K+ CHANNELS

A class Ib antiarrhythmic drug, mexiletine (100 mu M) significantly shortened the action potential duration (APD) of guinea-pig ventricular muscles and this effect was completely abolished in the presence of glibenclamide (50 mu M), a blocker of the ATP-sensitive K+ channel (K-ATP). Mexiletine significantly increased the open probability of uridine diphosphate-primed K-ATP channels, recorded in inside-out patches of the ventricular cells. The results suggest that mexiletine shortens the APD of ventricular muscles, at least in part, via activation of K-ATP.