title: Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K+ channel subunit.
abstract: G protein-gated inwardly rectifying K+ (GIRK) channels, which are important regulators of membrane excitability both in heart and brain, appear to function as heteromultimers. GIRK1 is unique in the GIRK channel family in that although it is by itself inactive, it can associate with the other family members (GIRK2-GIRK5) to enhance their activity and alter their single-channel characteristics. By generating a series of chimeras, we identified a phenylalanine residue, F137, in the pore region of GIRK1 that critically controls channel activity. F137 is found only in GIRK1, while the remaining GIRK channels possess a conserved serine residue in the analogous position. The single-point mutant GIRK4(S143F) behaved as a GIRK1 analog, forming multimers with GIRK2, GIRK4, or GIRK5 channels that exhibited prolonged single-channel open-time duration and enhanced activity compared with that of homomultimers. Expression of the corresponding GIRK1 (F137S) mutant alone resulted in appreciable channel activity with novel characteristics that was further enhanced upon coexpression with other GIRK subunits. Thus, although the F137 residue renders the GIRK1 subunit inactive, when combined with other GIRK heteromeric partners it alters their gating and contributes to their enhanced activity.
authors.affiliation: Department of Physiology and Biophysics, Mount Sinai School of Medicine, City University of New York, NY 10029, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Chan
authors.forename: J L
authors.initials: JL
authors.lastname: Sui
authors.forename: M
authors.initials: M
authors.lastname: Vivaudou
authors.forename: D E
authors.initials: DE
authors.lastname: Logothetis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D046911:Macromolecular Substances; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D010649:Phenylalanine; D017354:Point Mutation; D015221:Potassium Channels / Q000096:biosynthesis / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D046911:Macromolecular Substances; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins; D010649:Phenylalanine; D019204:GTP-Binding Proteins