Effects of calcium antagonistic drugs on the electrical activity of rabbit sino-atrial node.

The effects of several calcium antagonistic drugs (slow channel blockers), mesudipine, FR-34235 (nilvadipine), nifedipine, and verapamil, were compared on the naturally-occurring slow action potentials (APs) of the isolated spontaneously-contracting sinoatrial (SA)-node of the rabbit. Mesudipine, at 1 X 10(-8) M, had little or no effect on the AP parameters and beating frequency. At 1 X 10(-7) M, mesudipine depressed the amplitude, + Vmax and frequency of the APs. A higher concentration of mesudipine (3 X 10(-7) M) completely blocked the slow APs. The concentration of FR-34235 required for 50% depression of Vmax was 3 X 10(-8) M, and complete block required 1 X 10(-7) M. The verapamil and nifedipine concentrations required for complete block were 1 X 10(-6) M and 1 X 10(-7) M, respectively. The cells blocked by these drugs were depolarized to about -40 mV. Cells blocked and depolarized by the drugs responded to intensive field stimulation with a transient after-hyperpolarization, followed by damped oscillations. When [Ca]o was elevated from 1.8 mM to 5.4 mM, full block required a higher concentration of mesudipine (1 X 10(-6)M) and FR-34235 (1 X 10(-6)M). The order of potency of the drugs tested was: nifedipine = FR-34235 greater than mesudipine greater than verapamil. The effects of mesudipine, FR-34235, and nifedipine were easily reversible upon washout for 10 min, whereas those of verapamil required longer periods. The results indicate that the slow channel blockers, mesudipine, FR-34235, nifedipine, and verapamil depress the APs and automaticity of the SA-node.