EFFECTS OF DIVALENT-CATIONS ON THE E-4031-SENSITIVE REPOLARIZATION CURRENT, I-KR, IN RABBIT VENTRICULAR MYOCYTES

The effects of divalent cations on the E-4031-sensitive repolarization current (I-Kr) were studied in single ventricular myocytes isolated f rom rabbit hearts. One group of divalent cations (Cd2+, Ni2+, Co2+, an d Mn2+) produced a rightward shift of the I-Kr activation curve along the voltage axis, increased the maximum I-Kr amplitude (i.e., relieved the apparent inward rectification of the channel), and accelerated I- Kr tail current kinetics. Another group (Ca2+, Mg2+ and Sr2+) had rela tively little effect on I-Kr. The only divalent cation that blocked I- Kr was Zn2+ (0.1-1 mM). Under steady-state conditions, Ba2+ caused a s ubstantial block of I-K1, as previously reported. However, block by Ba 2+ was time dependent, which precluded a study of Ba2+ effects on I-Kr . We conclude that the various effects of the divalent cations can be attributed to interactions with distinct sites associated with the rec tification and/or inactivation mechanism of the channel.