Bepridil Block of Recombinant Human Cardiac IKs Current Shows a Time-Dependent Unblock

Whole-cell patch-clamp techniques were employed to examine the effects of bepridil, a Ca 2 + channel blocker with Vaughan Williams class III action, on a slow component of cardiac delayed rectifier K + current (I K s ), which was reconstituted in HEK293 cells by transfecting KCNQI and KCNEI. Micromolar bepridil inhibited tail currents carried by KCNQI/KCNEI channels in a concentration-dependent manner (IC 5 0 = 5.3 ′ 0.7 μM at -40 mV from 1000 milliseconds test pulse). When the effect of the drug was examined with a short test pulse protocol (250 milliseconds), IC 5 0 became two-fold smaller than that measured with 1000 milliseconds test pulse (2.5 ′ 0.8 μM). The envelope-of-tails protocol was used to assess how the duration of depolarizing pulse affects the drug action on the outward KCNQI/KCNEI channel current. The drug significantly inhibited tail currents more potently during shorter pulses (