A kinetic study of effects of propranolol and N-propylajmaline on the rate of rise of action potential in guinea pig papillary muscles.

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In isolated guinea pig papillary muscles driven at 1 Hz, propranolol in the concentrations of 10-6, 2 × l0-6 and 5 × 10-6 g/ml and N-propylajmaline (NAP) in the concentrations of 2 × 10-7, 5 × 10-7 and 10-6 g/ml both depressed dose-dependently the maximum rate of rise of action potential (Vmax) without affecting resting potential. With a rise in driving frequency from 0.25 to 5 Hz, Vmax was reduced progressively both in propranolol and NPA-treated preparations but such was slight in the control. Comparison of effects of both drugs in a concentration which exerted a similar extent of depression of Vmax at 1 Hz revealed that propranolol usually exerted less depression at lower frequencies and a greater depression at higher frequencies than NPA. Vmax depressed under the influence of propranolol was recovered toward the pre-drug level in the first response after a pause in stimulation with rate constants of 0.081 to 0.116 sec-1. A kinetic model was constructed on the basis of assumption that drug molecules were taken up to the site where they affect the sodium carrying system at the very beginining of excitation and were released during diastolic intervals with the rate constant of the recovery. Two modifications of the model are presented to elucidate the effects of both drugs.
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