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

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Abstract
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 × 10−8 M, had little or no effect on the AP parameters and beating frequency. At 1 × 10−7 M, mesudipine depressed the amplitude, + V̇max and frequency of the APs. A higher concentration of mesudipine (3 × 10−7 M) completely blocked the slow APs. The concentration of FR‐34235 required for 50% depression of V̇max was 3 × 10−8 M, and complete block required 1 × 10−7 M. The verapamil and nifedipine concentrations required for complete block were 1 × 10−6 M and 1 × 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 × 10−6 M) and FR‐34235 (1 × 10−6 M). The order of potency of the drugs tested was: nifedipine = FR‐34235 > mesudipine > 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.