INHIBITION OF AN INWARD RECTIFIER POTASSIUM CHANNEL (KIM2.3) BY G-PROTEIN BETA-GAMMA-SUBUNITS

The molecular basis of G-protein inhibition of inward rectifier K+ cur rents was examined by co-expression of G-proteins and cloned Kir2 chan nel subunits in Xenopus oocytes, Channels encoded by Kir2.3 (HRK1/HIR/ BIRK2/BIR11) were completely suppressed by co-expression with G-protei n beta gamma subunits, whereas channels encoded by Kir2.1 (IRK1), whic h shares 60% amino acid identity with Kir2.3, were unaffected, Co-expr ession of G alpha(il) and G alpha(q) subunits also partially suppresse d Kir2.3 currents, but G alpha(t), G alpha(s), and a constitutively ac tive mutant of G alpha(il) (Q204L) were ineffective. G beta gamma and Kir2.3 subunits were co-immunoprecipitated using an anti-Kir2.3 antibo dy. Direct binding of G-protein beta gamma subunits to fusion proteins containing Kir2.3 N terminus, but not to fusion proteins containing K ir2.1 N terminus, was also demonstrated, The results are consistent wi th suppression of Kir2.3 currents resulting from a direct protein-prot ein interaction between the channel and G-protein beta gamma subunits, When Kir2.1 and Kir2.3 subunits were coexpressed, the G-protein inhib itory phenotype of Kir2.3 was dominant, suggesting that co-expression of Kir2.3 with other Kir subunits might give rise to novel G-protein-i nhibitable inward rectifier currents.