Electrophysiological effect of disopyramide on rabbit sinus node cells.

The effects of disopyramide on the membrane potentials and currents of rabbit sinus node cells were studied using the conventional microelectrode and voltage clamp methods. Disopyramide (5 and 10 micrograms/m1) produced a negative chronotropic effect, and decreased the maximum rate of depolarization, the overshoot potential and the maximum diastolic potential. The action potential duration at half-amplitude was prolonged, and the slope of diastolic depolarization was reduced. In the voltage clamp experiments, disopyramide (10 and 50 micrograms/m1) reduced the potassium outward current (IK) without changing its kinetics. Disopyramide reduced the slow inward current Isi and increased the recovery time constant of Isi. The hyperpolarization-activated current (Ih) was also decreased by the drug. From these results, it is concluded that disopyramide has a depressant effect on the electrical activity of sinus node cells by mediating depression of IK, Isi and Ih.