Effects of Guanfu Base G on the Kinetics of Use‐dependent Block in Maximum Upstroke Velocity in Guinea‐pig Isolated Papillary Muscles

Abstract

The use-dependent block in the maximum upstroke velocity (Vmax) caused by Guanfu base G, a new diterpene alkaloid, was investigated in isolated papillary muscles of guinea-pigs. Guanfu base G (1–8 μM) produced a concentration-dependent decrease in Vmax and action potential amplitude, but had no effect on the resting potential and duration of the action potential. In the presence of Guanfu base G (4 and 8 μM), trains of stimuli at interstimulus intervals ranging from 4800 to 300 ms, led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequencies. The onset rate constants of use-dependent Vmax blocked by Guanfu base G (at interstimulus intervals of 300 ms) were 0.0748 ± 0.0046 AP−1 and 0.0767 ± 0.0041 AP−1 at 4 and 8 μM, respectively. The time constants for the recovery of Vmax from use-dependent block were 66.3 ± 6.5 and 68.5 ± 4.8 s, respectively. These findings suggest that Guanfu base G is a sodium channel-blocking drug with slow kinetics. The characteristic of a marked use-dependent Vmax block by Guanfu base G might be of benefit in the prevention and treatment of arrhythmias.