ACTIVATION OF G-PROTEIN-COUPLED INWARD RECTIFIER K-PROTEIN BETA-GAMMA-SUBUNITS WITH CELL-MEMBRANE( CHANNELS IN BRAIN NEURONS REQUIRES ASSOCIATION OF G)

In cultured noradrenergic neurons from the rat locus coeruleus, applic ation of recombinant G protein beta(1) gamma(2) subunits (30 nM) to th e cytoplasmic side induced single channel activity similar to the soma tostatin-induced single channel activity of G protein-coupled inward r ectifier potassium channels (K-ir (G)). In contrast, recombinant GTP g amma S-activated, myristoylated alpha(i2) (100 nM) did not activate th is brain K-ir (G). Application of beta(1) gamma(2)C68S (30 nM or 150 n M), in which the cysteine residue fourth from the carboxyl terminus of gamma 2 was replaced by serine, failed to activate the brain K-ir(G). This mutant lacks prenylation which is required for the association o f beta gamma subunit with the cell membrane, Thus, our results suggest that the association of beta gamma subunit with the cell membrane is a prerequisite for activating K-ir(G) channels.