Molecular mechanism and functional significance of the MinK control of the KvLQT1 channel activity

Georges Romey, Bernard Attali, Christophe Chouabe, Ilane Abitbol, Eric Guillemare, Jacques Barhanin, Michel Lazdunski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

The very slowly activating delayed rectifier K- channel I(Ks) is essential for controlling the repolarization phase of cardiac action potentials and K- homeostasis in the inner ear. The I(Ks) 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.

Original languageEnglish
Pages (from-to)16713-16716
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number27
DOIs
StatePublished - 4 Jul 1997
Externally publishedYes

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