Referenced in: none

Automatically associated channels: Kv7.1 , Slo1

Title: Molecular impact of MinK on the enantiospecific block of I(Ks) by chromanols.

Authors: C Lerche, G Seebohm, C I Wagner, C R Scherer, L Dehmelt, I Abitbol, U Gerlach, J Brendel, B Attali, A E Busch

Journal, date & volume: Br. J. Pharmacol., 2000 Dec , 131, 1503-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11139424

Abstract
Slowly activating I:(Ks) (KCNQ1/MinK) channels were expressed in Xenopous: oocytes and their sensitivity to chromanols was compared to homomeric KCNQ1 channels. To elucidate the contribution of the ss-subunit MinK on chromanol block, a formerly described chromanol HMR 1556 and its enantiomer S5557 were tested for enantio-specificity in blocking I:(Ks) and KCNQ1 as shown for the single enantiomers of chromanol 293B. Both enantiomers blocked homomeric KCNQ1 channels to a lesser extent than heteromeric I:(Ks) channels. Furthermore, we expressed both WT and mutant MinK subunits to examine the involvement of particular MinK protein regions in channel block by chromanols. Through a broad variety of MinK deletion and point mutants, we could not identify amino acids or regions where sensitivity was abolished or strikingly diminished (>2.5 fold). This could indicate that MinK does not directly take part in chromanol binding but acts allosterically to facilitate drug binding to the principal subunit KCNQ1.