A Switch Mechanism for Gβγ Activation of IKACh

• Published in: The Journal of biological chemistry Vol. 275; no. 38; pp. 29709 - 29716
• Main Authors: Medina, Igor, Krapivinsky, Grigory, Arnold, Susanne, Kovoor, Pramesh, Krapivinsky, Luba, Clapham, David E.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 22.09.2000
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M004989200

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 Gβγ 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 Gβγ. 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 Gβγ gating of the channel complex.