title: Kvbeta2 inhibits the Kvbeta1-mediated inactivation of K+ channels in transfected mammalian cells.
abstract: Cloned auxiliary beta-subunits (e.g. Kvbeta1) modulate the kinetic properties of the pore-forming alpha-subunits of a subset of Shaker-like potassium channels. Coexpression of the alpha-subunit and Kvbeta2, however, induces little change in channel properties. Since more than one beta-subunit has been found in individual K+ channel complexes and expression patterns of different beta-subunits overlap in vivo, it is important to test the possible physical and/or functional interaction(s) between different beta-subunits. In this report, we show that both Kvbeta2 and Kvbeta1 recognize the same region on the pore-forming alpha-subunits of the Kv1 Shaker-like potassium channels. In the absence of alpha-subunits the Kvbeta2 polypeptide interacts with additional beta-subunit(s) to form either a homomultimer with Kvbeta2 or a heteromultimer with Kvbeta1. When coexpressing alpha-subunits and Kvbeta1 in the presence of Kvbeta2, we find that Kvbeta2 is capable of inhibiting the Kvbeta1-mediated inactivation. Using deletion analysis, we have localized the minimal interaction region that is sufficient for Kvbeta2 to associate with both alpha-subunits and Kvbeta1. This mapped minimal interaction region is necessary and sufficient for inhibiting the Kvbeta1-mediated inactivation, consistent with the notion that the inhibitory activity of Kvbeta2 results from the coassembly of Kvbeta2 with compatible alpha-subunits and possibly with Kvbeta1. Together, these results provide biochemical evidence that Kvbeta2 may profoundly alter the inactivation activity of another beta-subunit by either differential subunit assembly or by competing for binding sites on alpha-subunits, which indicates that Kvbeta2 is capable of serving as an important determinant in regulating the kinetic properties of K+ currents.
authors.affiliation: Department of Physiology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D046911:Macromolecular Substances; D008322:Mammals; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008961:Models, Structural; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D014162:Transfection
chemical_list: D017931:DNA Primers; D046911:Macromolecular Substances; D015221:Potassium Channels; D011994:Recombinant Proteins