PubMed 10900209

Referenced in: none

Automatically associated channels: Kir2.1 , Kir2.2 , Kir2.4 , Kir3.1 , Kir3.2 , Kir3.4 , Slo1

Title: A switch mechanism for G beta gamma activation of I(KACh).

Authors: I Medina, G Krapivinsky, S Arnold, P Kovoor, L Krapivinsky, D E Clapham

Journal, date & volume: J. Biol. Chem., 2000 Sep 22 , 275, 29709-16

PubMed link:

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.