Frequency- and voltage-dependent effects of changrolin on maximal upstroke velocity of action potentials in guinea pig papillary muscles

Changrolin (CRL) is a new antiarrhythmic drug originated in China in 1970s. The effects of CRL on maximal upstroke velocity (Vmax) of action potentials were studied with standard microelectrode and computer in guinea pig papillary muscles. CRL depressed the Vmax. This effect was dependent on the rate of stimulations. The onset of use-dependent depression was monoexponential and dependent on drug concentration and rate of stimulations. The rate of recovery from use-dependent depression also followed a single exponential time course. CRL shifted the curve relating normalized Vmax to membrane potential in the hyperpolarizing direction. The onset rate was 0.156 +/- 0.025 AP-1 (RDB 50%), and offset rate (tau r) was 4.7 +/- 0.9 s. These suggest that CRL belongs to class Ia antiarrhythmic drugs.