Stereoselective block of the hERG potassium channel by the Class Ia antiarrhythmic drug disopyramide.

ABSTRACT: Potassium channels encoded by human Ether-à-go-go-Related Gene (hERG) are inhibited by diverse cardiac and non-cardiac drugs. Disopyramide is a chiral Class Ia antiarrhythmic that inhibits hERG at clinical concentrations. This study evaluated effects of disopyramide enantiomers on hERG current (I_hERG) from hERG expressing HEK 293 cells at 37 °C. S(+) and R(-) disopyramide inhibited wild-type (WT) I_hERG with IC₅₀ values of 3.9 µM and 12.9 µM respectively. The attenuated-inactivation mutant N588K had little effect on the action of S(+) disopyramide but the IC₅₀ for the R(-) enantiomer was ~ 15-fold that for S(+) disopyramide. The enhanced inactivation mutant N588E only slightly increased the potency of R(-) disopyramide. S6 mutation Y652A reduced S

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC11604869 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature