title: Coupling of voltage sensing to channel opening reflects intrasubunit interactions in kv channels.
abstract: Voltage-gated K(+) channels play a central role in the modulation of excitability. In these channels, the voltage-dependent movement of the voltage sensor (primarily S4) is coupled to the (S6) gate that opens the permeation pathway. Because of the tetrameric structure, such coupling could occur within each subunit or between adjacent subunits. To discriminate between these possibilities, we analyzed various combinations of a S4 mutation (R401N) and a S6 mutation (P511G) in hKv1.5, incorporated into tandem constructs to constrain subunit stoichiometry. R401N shifted the voltage dependence of activation to negative potentials while P511G did the opposite. When both mutations were introduced in the same alpha-subunit of the tandem, the positive shift of P511G was compensated by the negative shift of R401N. With each mutation in a separate subunit of a tandem, this compensation did not occur. This suggests that for Kv channels, the coupling between voltage sensing and gating reflects primarily an intrasubunit interaction.
authors.affiliation: Laboratory for Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, Antwerp 2610, Belgium.
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Labro
authors.forename: Adam L
authors.initials: AL
authors.lastname: Raes
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Snyders
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D011994:Recombinant Proteins