Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

Abstract

The correlation between the steady state and non-steady state depression of .ovrhdot.Vmax by 50 .mu.M disopyramide [an antiarrhythmic drug] was investigated in 2.7, 5.4 and 8.1 mM [K+]o using isolated guinea pig papillary muscle. An elevation of [K+]o from 2.7 to 8.1 mM strengthened the depressant action of the drug on .ovrhdot.Vmax (steady state) at 1-5 Hz, but attenuated this action at 0.05 and 0.1 Hz. The .ovrhdot.Vmax-membrane potential (Vm) relationship (steady state) was examined at stimulation rates of 0.1 and 1 Hz by increasing [K+]o from 2.7 to 19 mM. The drug shifted the normalized .ovrhdot.Vmax-Vm curve at 1 Hz in a hyperpolarizing direction, but shifted the curve at 0.1 Hz upward at Vm between -90 and -65 mV without a shift along the Vm axis. The recovery process of .ovrhdot.Vmax (non-steady state) was examined by introducing premature stimuli or by interrupting the basic stimulus of 1 Hz for a certain period. The control recovery processes in 3 [K+]o were approximated by a triple exponential function (the earliest, intermediate and latest components). The drug slowed the intermediate component, but accelerated the latest one (the earliest component was situated within the refractory period) when [K+]o was elevated from 2.7 to 8.1 mM. The finding that the elevation of [K+]o attenuated the depressant action of disopyramide on the .ovrhdot.Vmax at 0.05 and 0.1 Hz and accelerated the recovery process of .ovrhdot.Vmax at long diastolic intervals of > 10 s was unique.