Calcium Channel Inhibitor, Verapamil, Inhibits the Voltage-Dependent K⁺ Channels in Rabbit Coronary Smooth Muscle Cells

Abstract

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 μM. 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 μM⁻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 μM) 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.