Rate-dependent depression of maximal rate of depolarization in guinea pig papillary muscle action potentials by changrolin

The rate-dependent block (RDB) of changrolin on the maximal rate of depolarization (Vmax) of action potentials was studied in guinea pig right ventricular papillary muscles. The result was compared with that of class IA (quinidine), IB (mexiletine) and IC (lorcainide) drugs to approach the subclassification of changrolin, by using standard microelectrode techniques with computer. Mexiletine exhibited the fastest response in the onset rate of RDB. Vmax reached 61% of its final value by the second beat during a train of stimuli. In response to a similar train of stimuli, quinidine, lorcainide and changrolin produced exponential falls of Vmax with the constants of -0.143, -0.085 and -0.051 AP-1 (AP = action potentials), respectively. Time constants of recovery for mexiletine, quinidine, lorcainide and changrolin were estimated as 1.58, 9.06, 13.37 and 55.16 s. These suggest that the kinetics of RDB of changrolin are similar to those of IC drugs.