ABSTRACT
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 [fKvl.4deltaN], an N-terminal-deleted mutant of the ferret Kvl.4 potassium channel. Measurements were made using a two electrode voltage clamp technique with channels expressed stably in Xenopus oocytes. The fKvl.4deltaN currents displayed slow inactivation, with a half-inactivation potential of-38.38 mV and slow recovery from inactivation [T = 1.90 seconds at -90 mV]. The fKv 1.4deltaN 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 fKvl.4deltaN currents with 50% inhibitory concentration [IC[50] values of 260.71 +/- 18.50 micromol/L and 241.04 +/- 23.06 micromol/L, respectively. Verapamil accelerated the C-type inactivation rate and slowed recovery of the fKv 1.4delta N channel, while shifting the steady activation curve to the right. Blockade of fKvl.4deltaN currents by diltiazem was similar to that of verapamil, but diltiazem accelerated the decay rate of inactivation of fKv 1.4 deltaN 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 fKv 1.4 deltaN channel in the open state