Yoshihiro Yumoto

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 Ca2+ channel blocker with Vaughan Williams class III action, on a slow component of cardiac delayed rectifier K+ current (IKs), which was reconstituted in HEK293 cells by transfecting KCNQ1 and KCNE1. Micromolar bepridil inhibited tail currents carried by KCNQ1/KCNE1 channels in a concentration-dependent manner (IC50 = 5.3 ± 0.7 &mgr;M at −40 mV from 1000 milliseconds test pulse). When the effect of the drug was examined with a short test pulse protocol (250 milliseconds), IC50 became two-fold smaller than that measured with 1000 milliseconds test pulse (2.5 ± 0.8 &mgr;M). The envelope-of-tails protocol was used to assess how the duration of depolarizing pulse affects the drug action on the outward KCNQ1/KCNE1 channel current. The drug significantly inhibited tail currents more potently during shorter pulses (<600 milliseconds). Bepridils block was therefore time dependent, and its binding affinity to the channel was greater in the closed state channel, as evidenced by unblocking during prolonged depolarization. These properties of channel blockade appear to underscore the mechanism of bepridils effect on IKs current.

Preventive Effect of Amiodarone on VT/VF Events in ICD Patients with Structural Heart Diseases

Background: Although amiodarone (AMD) is applied for implantable cardioverterdefibrillator (ICD) patients to reduce VT/VF events, its actual benefit and long‐term efficacy are unclear. In the present study, we retrospectively evaluated the incidence of VT/VF events in ICD patients with and without AMD.