title: The electrically silent Kv6.4 subunit confers hyperpolarized gating charge movement in Kv2.1/Kv6.4 heterotetrameric channels.
abstract: The voltage-gated K(+) (Kv) channel subunit Kv6.4 does not form functional homotetrameric channels but co-assembles with Kv2.1 to form functional Kv2.1/Kv6.4 heterotetrameric channels. Compared to Kv2.1 homotetramers, Kv6.4 exerts a ~40 mV hyperpolarizing shift in the voltage-dependence of Kv2.1/Kv6.4 channel inactivation, without a significant effect on activation gating. However, the underlying mechanism of this Kv6.4-induced modulation of Kv2.1 channel inactivation, and whether the Kv6.4 subunit participates in the voltage-dependent gating of heterotetrameric channels is not well understood. Here we report distinct gating charge movement of Kv2.1/Kv6.4 heterotetrameric channels, compared to Kv2.1 homotetramers, as revealed by gating current recordings from mammalian cells expressing these channels. The gating charge movement of Kv2.1/Kv6.4 heterotetrameric channels displayed an extra component around the physiological K(+) equilibrium potential, characterized by a second sigmoidal relationship of the voltage-dependence of gating charge movement. This distinct gating charge displacement reflects movement of the Kv6.4 voltage-sensing domain and has a voltage-dependency that matches the hyperpolarizing shift in Kv2.1/Kv6.4 channel inactivation. These results provide a mechanistic basis for the modulation of Kv2.1 channel inactivation gating kinetics by silent Kv6.4 subunits.
authors.affiliation: Laboratory for Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, CDE, Universiteitsplein 1, Antwerpen, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Bocksteins
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Labro
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Snyders
authors.forename: Durga P
authors.initials: DP
authors.lastname: Mohapatra
mesh_terms: D002461:Cell Line, Transformed; D004560:Electricity; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism*; D051669:Shab Potassium Channels / Q000378:metabolism*
chemical_list: C496988:KCNB1 protein, human; D021122:Protein Subunits; D051669:Shab Potassium Channels; D011188:Potassium