title: A switch mechanism for G beta gamma activation of I(KACh).
abstract: G protein-gated inwardly rectifying potassium (GIRK) channels are a family of K(+)-selective ion channels that slow the firing rate of neurons and cardiac myocytes. GIRK channels are directly bound and activated by the G protein G beta gamma subunit. As heterotetramers, they comprise the GIRK1 and the GIRK2, -3, or -4 subunits. Here we show that GIRK1 but not the GIRK4 subunit is phosphorylated when heterologously expressed. We found also that phosphatase PP2A dephosphorylation of a protein in the excised patch abrogates channel activation by G beta gamma. Experiments with the truncated molecule demonstrated that the GIRK1 C-terminal is critical for both channel phosphorylation and channel regulation by protein phosphorylation, but the critical phosphorylation sites were not located on the C terminus. These data provide evidence for a novel switch mechanism in which protein phosphorylation enables G beta gamma gating of the channel complex.
authors.affiliation: Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: I
authors.initials: I
authors.lastname: Medina
authors.forename: G
authors.initials: G
authors.lastname: Krapivinsky
authors.forename: S
authors.initials: S
authors.lastname: Arnold
authors.forename: P
authors.initials: P
authors.lastname: Kovoor
authors.forename: L
authors.initials: L
authors.lastname: Krapivinsky
authors.forename: D E
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats
chemical_list: C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D015221:Potassium Channels; D020962:Heterotrimeric GTP-Binding Proteins