Effects of L-type Calcium Channel Antagonists Verapamil and Diltiazem on fKv1.4ΔN Currents in Xenopus oocytes

The goal of this study was to determine the effects of the L-type calcium channel blockers verapamil and diltiazem on the currents of voltage-gated potassium channel (fKv1.4 Delta N), an N-terminal-deleted mutant of the ferret Kv1.4 potassium channel. Measurements were made using a two electrode voltage clamp technique with channels expressed stably in Xenopus oocytes. The fKv1.4 Delta N currents displayed slow inactivation, with a half-inactivation potential of -38.38 mV and slow recovery from inactivation (tau = 1.90 seconds at -90 mV). The fKv1.4 Delta N currents exhibited state-dependent blockade by both drugs, and the inhibition was frequency-, voltage-, and concentration-dependent, consistent with open channel block. Verapamil and diltiazem blocked fKv1.4 Delta N currents with 50% inhibitory concentration (IC50) values of 260.71 +/- 18.50 mu mol/L and 241.04 +/- 23.06 mu mol/L, respectively. Verapamil accelerated the C-type inactivation rate and slowed recovery of the fKv1.4 Delta N channel, while shifting the steady activation curve to the right. Blockade of fKv1.4 Delta N currents by diltiazem was similar to that of verapamil, but diltiazem accelerated the decay rate of inactivation of fKv1.4 Delta N currents without modifying the kinetics of current activation. The present results suggest that verapamil and diltiazem accelerate the C-type inactivation and slow the recovery of the fKv1.4 Delta N channel in the open state.