Effect of bepridil on membrane currents of rabbit sinoatrial node cells

Effect of 1-[3-isobutoxy-2-(benzylphenyl) amino]propyl pyrrolidine hydrochloride (bepridil), a new antianginal agent, on membrane potentials and membrane currents of sinoatrial node cells of rabbits was examined using conventional microelectrode and double microelectrode voltage clamp methods. Bepridil at a concentration of 10 mumol/l caused an increase in spontaneous cycle length, and a decrease in maximum rate of rise of the action potential and action potential amplitude. The rate of diastolic depolarization (phase 4) was also decreased by the drug. In the voltage clamp experiment, bepridil reduced both the slow inward current (Isi) and the hyperpolarization activated current (Ih), and increased the recovery time constant of Isi, whereas the time-dependent potassium current (IK) was not altered significantly. The major effect, however, was the reduction of Isi. These electrophysiological findings suggest that bepridil has a depressant effect on the electrical activity of sinoatrial node mainly by mediating the depression of slow channel.