EFFECTS OF DISOPYRAMIDE ON THE MAXIMUM RATE OF RISE OF ACTION POTENTIAL (Vmax) IN GUINEA-PIG PAPILLARY MUSCLES

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The correlation between the steady state and non-steady state depression of Vmax by 50 μM disopyramide was investigated in 2.7, 5.4 and 8.1 mM [K+]o using isolated guinea-pig papillary muscles. An elevation of [K+]0 from 2.7 to 8.1 mM strengthened the depressant action of the drug on Vmax (steady state) at 1 to 5 Hz, but attenuated this action at 0.05 and 0.1 Hz. The 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 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 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 three [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 Vmax at 0.05 and 0.1 Hz and accelerated the recovery process of Vmax at long diastolic intervals of more than 10 sec was quite unique.
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