title: Molecular mechanism and functional significance of the MinK control of the KvLQT1 channel activity.
abstract: The very slowly activating delayed rectifier K+ channel IKs is essential for controlling the repolarization phase of cardiac action potentials and K+ homeostasis in the inner ear. The IKs channel is formed via the assembly of two transmembrane proteins, KvLQT1 and MinK. Mutations in KvLQT1 are associated with a long QT syndrome that causes syncope and sudden death and also with deafness. Here, we show a new mode of association between ion channel forming subunits in that the cytoplasmic C-terminal end of MinK interacts directly with the pore region of KvLQT1. This interaction reduces KvLQT1 channel conductance from 7.6 to 0.58 picosiemens. However, because MinK also reveals a large number of previously silent KvLQT1 channels (x 60), the overall effect is a large increase (x 4) in the macroscopic K+ current. Conformational changes associated with the KvLQT1/MinK association create very slow and complex activation kinetics without much alteration in the deactivation process. Changes induced by MinK have an essential regulatory role in the development of this K+ channel activity upon repetitive electrical stimulation with a particular interest in tachycardia.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
authors.forename: G
authors.initials: G
authors.lastname: Romey
authors.forename: B
authors.initials: B
authors.lastname: Attali
authors.forename: C
authors.initials: C
authors.lastname: Chouabe
authors.forename: I
authors.initials: I
authors.lastname: Abitbol
authors.forename: E
authors.initials: E
authors.lastname: Guillemare
authors.forename: J
authors.initials: J
authors.lastname: Barhanin
authors.forename: M
authors.initials: M
authors.lastname: Lazdunski
mesh_terms: D000200:Action Potentials; D000818:Animals; D019556:COS Cells; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D007700:Kinetics; D008958:Models, Molecular; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D014162:Transfection
chemical_list: D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk)