Activation of G protein‐coupled inward rectifier K+ channels in brain neurons requires association of G protein βγ subunits with cell membrane

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Abstract
In cultured noradrenergic neurons from the rat locus coeruleus, application of recombinant G protein β 1 γ 2 subunits (30 nM) to the cytoplasmic side induced single channel activity similar to the somatostatin-induced single channel activity of G protein-coupled inward rectifier potassium channels (Kir (G)). In contrast, recombinant GTPγS-activated, myristoylated α i2 (100 nM) did not activate this brain Kir (G). Application of β 1 γ 2C68S (30 nM or 150 nM), in which the cysteine residue fourth from the carboxyl terminus of γ 2 was replaced by serine, failed to activate the brain Kir(G). This mutant lacks prenylation which is required for the association of βγ subunit with the cell membrane. Thus, our results suggest that the association of βγ subunit with the cell membrane is a prerequisite for activating Kir(G) channels.