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

Abstract

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 μM, prolonged the 90% action potential duration (APD 90) without changing the maximum rate of phase 0 depolarization (V max) (class 3 action), whereas disopyramide, 20 μM, reduced V max (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 μM, enhanced the rate-dependent reduction in V max only in 8.1 mM [K +] 0. Neither concentration of disopyramide altered the recovery kinetics of APD 90 in the premature responses in three [K +] 0, but slowed that of V max only in 8.1 mM [K +] 0. These results indicate that the manifestation of the 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 case of the class 1 action.