G protein-activated inwardly rectifying K+ channel subunits GIRK1 (Kir 3.1), GIRK2 (Kir 3.2), and CIR (Kir 3.4) were expressed individually or in combination in Xenopus oocytes and CHO cells. GIRK1 coexpressed with CIR or GIRK2, produced currents up to 10-fold larger than any of the subunits expressed alone. No such clear synergistic effects were observed upon coexpression of CIR/GIRK2 under the same conditions. Coexpression of G protein βγ (mGβ1γ2) increased the current through GIRK1/GIRK2 and GIRK2 channels. Gβγ subunits purified from bovine brain, increased channel activity 50–1000-fold in patches from cells expressing GIRK1/GIRK2 or GIRK2 alone. The single GIRK1/GIRK2 channels resembled previously described neuronal G protein-gated K+ channels. In contrast, single GIRK2 channels were short-lived and unlike any previously described neuronal K+ channel. We propose that some neuronal G protein-activated inward rectifier K+ channels may be formed by a GIRK1/GIRK2 heteromultimer and that Gβγ activation may involve both subunits.
