A switch mechanism for G beta gamma activation of I(KACh).
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.
Medina
I
I
Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Krapivinsky
G
G
Arnold
S
S
Kovoor
P
P
Krapivinsky
L
L
Clapham
D E
DE
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
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