Role of the S6 C-terminus in KCNQ1 channel gating.

Role of the S6 C-terminus in KCNQ1 channel gating. Research Abstract Details 

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Role of the S6 C-terminus in KCNQ1 channel gating. Abstract Text:

Inge R Boulet,Alain J Labro,Adam L Raes,Dirk J Snyders,Inge R Boulet,Alain J Labro,Adam L Raes,Dirk J Snyders,Inge R Boulet,Alain J Labro,Adam L Raes,Dirk J Snyders,

Co-assembly of KCNQ1 alpha-subunits with KCNE1 beta-subunits results in the channel complex underlying the cardiac IKs current in vivo. Like other voltage-gated K+ channels, KCNQ1 has a tetrameric configuration. The S6 segment of each subunit lines the ion channel pore with the lower part forming the activation gate. To determine residues involved in protein-protein interactions in the C-terminal part of S6 (S6T), alanine and tryptophan perturbation scans were performed from residue 348-362 in the KCNQ1 channel. Several residues were identified to be relevant in channel gating, as substitutions affected the activation and/or deactivation process. Some mutations (F351A and V355W) drastically altered the gating characteristics of the resultant KCNQ1 channel, to the point of mimicking the IKs current. Furthermore, mutagenesis of residue L353 to an alanine or a charged residue impaired normal channel closure upon hyperpolarization, generating a constitutively open phenotype. This indicates that the L353 residue is essential for stabilizing the closed conformation of the channel gate. These findings together with the identification of several LQT1 mutations in the S6 C-terminus of KCNQ1 underscore the relevance of this region in KCNQ1 and IKs channel gating.

Role of the S6 C-terminus in KCNQ1 channel gating. Publishing Authors By Initials

IR Boulet,AJ Labro,AL Raes,DJ Snyders,IR Boulet,AJ Labro,AL Raes,DJ Snyders,IR Boulet,AJ Labro,AL Raes,DJ Snyders,

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Role of the S6 C-terminus in KCNQ1 channel gating. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of physiology

VOLUME: 585

Page Numbers: 325-37

Journal Abbreviation: J. Physiol. (Lond.)

ISSN: 0022-3751

DAY: 11

MONTH: 10

YEAR: 2007

Role of the S6 C-terminus in KCNQ1 channel gating. Information

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LANGUAGE: eng

NlmUniqueID: 266262

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AFFILIATION: Laboratory for Molecular Biophysics, Pharmacology and Physiology, University of Antwerp, Department of Biomedical Sciences, Antwerp, Belgium.

Country: England

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MEDLINETA: J Physiol

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