摘要：We investigated the effect of the phenylalkylamine Ca2+ channel inhibitor verapamil on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Verapamil reduced the Kv current amplitude in a concentration-depenent manner. The apparent K d value for Kv channel inhibition was 0.82 μ M . Although verapamil had no effect on the activation kinetics, it accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation by verapamil were 2.20±0.02 μ M −1 s−1, and 1.79±0.26 s−1, respectively. The steady-state activation and inactivation curves were unaffected by verapamil. The application of train pulses increased the verapamil-induced Kv channel inhibition. Furthermore, verapamil increased the recovery time constant, suggesting that the inhibitory effect of this agent was use-dependent. The inhibitory effect of verapamil was not affected by intracellular and extracellular Ca2+-free conditions. Another Ca2+ channel inhibitor, nifedipine (10 μ M ) did not affect the Kv current, and did not alter the inhibitory effect of verapamil. Based on these results, we concluded that verapamil inhibited Kv current in a state-, time-, and use-dependent manner, independent of Ca2+ channel inhibition.
