Functional expression and characterization of G-protein-gated inwardly rectifying K+ channels containing GIRK3

The G-protein-gated inwardly rectifying K+(GIRK) family of ion channels for m functional G beta gamma-sensitive channels as heteromultimers of GIRK1 an d either the GIRK2 or GIRK4 subunits. However, the homologous mouse brain G IRK3 clone failed to express in the earliest reported functional experiment s in Xenopus oocytes. We recloned the GIRK3 subunit from mouse brain and fo und that the new clone differed significantly from that originally reported . The functional aspects of GIRK3 were reinvestigated by expression in CHO cells. The single channel properties of GIRK1/GIRK3 were characterized and compared to those of the GIRK1/GlRK2 and GIRK1/GIRK4 channels. All three GI RK1/GIRKx combinations produced channels with nearly indistinguishable cond uctances and kinetics. The response of GIRK1/GIRK3 to G beta gamma in the 1 -47 nM range was examined and found to be indistinguishable from that of GI RK1/GIRK4 channels. We conclude that GIRK1, with either GIRK2, 3, or 4, giv es rise to heteromultimeric channels with virtually identical conductances, kinetics, and G beta gamma sensitivities.