Effects of disopyramide on transmembrane action potentials in guinea-pig papillary muscles

The effects of disopyramide on the transmembrane action potential in guinea-pig papillary muscles were studied with special reference to the dependence of the effects on the external concentrations of K+ ([K+]0), stimulation rates, and diastolic intervals. Disopyramide, 2 micrometer, prolonged the 90% action potential duration (ADP90) without changing the maximum rate of phase 0 depolarization (Vmax) (class 3 action), whereas disopyramide, 20 micrometer, reduced Vmax, (class 1 action). The class 3 action was prominent in 2.7 and 5.4 mM [K+]0, at 0.25--1 Hz, and so was the class 1 action in 8.1 mM [K+]0, at 2--5 Hz. Disopyramide, 20 micrometer, enhanced the rate-dependent reduction in Vmax only in 8.1 mM [K+]0. Neither concentration of disopyramide altered the recovery kinetics of APD90 in the premature responses in three [K+]0, but slowed that of Vmax only in 8.1 mM [K+]0. These results indicate that the manifestation of class 3 action of disopyramide is favored with low concentrations of the drug, low [K+]0, and low stimulation rates, whereas the reverse is true in the class of the class 1 action.