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Redox state dependency of HERG S631C channel pharmacology: relation to C‐type inactivation
Author(s) -
Ulens Chris,
Tytgat Jan
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01586-6
Subject(s) - herg , chemistry , astemizole , dofetilide , pharmacology , terfenadine , biophysics , stereochemistry , potassium channel , biology , medicine , qt interval
The S631C mutation in human ether‐à‐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. In this study, we report the relation between pharmacology and C‐type inactivation for HERG S631C channels. We demonstrate that HERG S631C in its reduced state is fully blocked by 1 μM astemizole, terfenadine and dofetilide, similar to wild‐type HERG channels. In contrast, oxidized HERG S631C is insensitive for these blockers. Our results suggest that an interaction with HERG channels in the inactivated state might be a common mechanism to a variety of drugs known to block HERG channels with high affinity.