Molecular impact of MinK on the enantiospecific block of I-Ks by chromanols

Slowly activating I-Ks (KCNQ1/MinK) channels were expressed in Xenopous ooc ytes and their sensitivity to chromanols was compared to homomeric KCNQ1 ch annels. To elucidate the contribution of the beta -subunit MinK on chromano l block, a formerly described chromanol HMR 1556 and its enantiomer S5557 w ere tested for enantio-specificity in blocking I-Ks and KCNQ1 as shown for the single enantiomers of chromanol 293B. Both enantiomers blocked homomeri c KCNQ1 channels to a lesser extent than heteromeric I-Ks channels. Further more, we expressed both WT and mutant MinK subunits to examine the involvem ent of particular MinK protein regions in channel block by chromanols. Thro ugh a broad variety of MinK deletion and point mutants, we could not identi fy amino acids or regions where sensitivity was abolished or strikingly dim inished (>2.5 fold). This could indicate that MinK does not directly take p art in chromanol binding but acts allosterically to facilitate drug binding to the principal subunit KCNQ1.