Depression of automaticity of the rabbit SA node by bepridil and nifedipine.

The effects of bepridil and nifedipine, newly developed Ca2+ antagonists, were studied on the spontaneous action potentials of the true pacemaker cell preparations (0.5 X 0.5 mm) obtained from the rabbit sino-atrial (SA) node. At the lower concentrations, bepridil (10(-6) M) and nifedipine (10(-8) M) decreased the spontaneous activity in accordance with the decrease of the maximum rate of rise of the action potential (Vmax), without changing the maximum diastolic potential (MDP) and the 50% action potential duration ( APD50 ). At the high concentrations, bepridil (5 X 10(-6) M) and nifedipine (5 X 10(-8) M) stopped the sinus automaticity with the depolarization of the MDP. The action potential could not be induced by the hyperpolarizing electrical stimulation in the presence of the higher concentration of these drugs. The results suggest that bepridil and nifedipine have a primary effect of the blocking action on the SA node slow channels, similar to the action of verapamil. This can account for their negative chronotropic action.