title: Biophysical characteristics of a new mutation on the KCNQ1 potassium channel (L251P) causing long QT syndrome.
abstract: The congenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by prolonged ventricular repolarization, syncope, and sudden death. Mutations causing LQTS have been identified in various genes that encode for ionic channels or their regulatory subunits. Several of these mutations have been reported on the KCNQ1 gene encoding for a potassium channel or its regulatory subunit (KCNE1). In this study, we report the biophysical characteristics of a new mutation (L251P) in the transmembrane segment 5 (S5) of the KCNQ1 potassium channel. Potassium currents were recorded from CHO cells transfected with either wild type or mutant KCNQ1 in the presence or in the absence of its regulatory subunit (KCNE1), using the whole-cell configuration of the patch clamp technique. Wild-type KCNQ1 current amplitudes are increased particularly by KCNE1 co-expression but no current is observed with the KCNQ1 (L251P) mutant either in the presence or in the absence of KCNE1. Coexpressing KCNE1 with equal amount of cDNAs encoding wild type and mutant KCNQ1 results in an 11-fold reduction in the amplitude of potassium currents. The kinetics of activation and inactivation and the activation curve are minimally affected by this mutation. Our results suggest that the dominant negative effect of the P251L mutation on KCNQ1 channel explains the prolonged repolarization in patients carrying this mutation.
authors.affiliation: Laval University, Faculty of Medicine, Sainte-Foy, QC G1K 7P4, Canada.
authors.forename: Dominic
authors.initials: D
authors.lastname: Deschênes
authors.forename: Said
authors.initials: S
authors.lastname: Acharfi
authors.forename: Valerie
authors.initials: V
authors.lastname: Pouliot
authors.forename: Robert
authors.initials: R
authors.lastname: Hegele
authors.forename: Andrew
authors.initials: A
authors.lastname: Krahn
authors.forename: Pascal
authors.initials: P
authors.lastname: Daleau
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chahine
mesh_terms: D000293:Adolescent; D000818:Animals; D001703:Biophysics / Q000379:methods*; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D051668:Delayed Rectifier Potassium Channels; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000151:congenital / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000187:drug effects* / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D014162:Transfection
chemical_list: D051668:Delayed Rectifier Potassium Channels; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated