Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation

The S631C mutation in human ether-a-go-go-related gene (HERG) channels has previously been reported to disrupt C-type inactivation and ion-selectivity when Cys-631 is in the oxidized state. Tn this study, we report the relati on between pharmacology and C-type inactivation for HERGS631C channels. We demonstrate that HEXGS631C in its reduced state is fully blocked by 1 mu M astemizole, terfenadine and dofetilide, similar to mild-type HERG channels. In contrast, oxidized HERGS631C is insensitive for these blockers, Our res ults suggest that an interaction with HERG channels in the inactivated stat e might be a common mechanism to a variety of drugs known to block HERG cha nnels with high affinity. (C) 2000 Federation of European Biochemical Socie ties.