Effects of Divalent Cations on the E-4031-Sensitive Repolarization Current, IKr, in Rabbit Ventricular Myocytes

AbstractThe effects of divalent cations on the E-4031-sensitive repolarization current (IKr) were studied in single ventricular myocytes isolated from rabbit hearts. One group of divalent cations (Cd2+, Ni2+, Co2+, and Mn2+) produced a rightward shift of the IKr activation curve along the voltage axis, increased the maximum IKr amplitude (i.e., relieved the apparent inward rectification of the channel), and accelerated IKr tail current kinetics. Another group (Ca2+, Mg2+ and Sr2+) had relatively little effect on IKr. The only divalent cation that blocked IKr was Zn2+ (0.1–1mM). Under steady-state conditions, Ba2+ caused a substantial block of IK1, as previously reported. However, block by Ba2+ was time dependent, which precluded a study of Ba2+ effects on IKr. We conclude that the various effects of the divalent cations can be attributed to interactions with distinct sites associated with the rectification and/or inactivation mechanism of the channel