GIRK3 has been shown to mediate interactions between GIRK channels and proteins that can regulate GIRK channel trafficking (sorting nexin 27, or SNX-27)36 and receptor coupling efficiency (regulator of G protein signaling 2, or RGS2)37. As GIRK3 is also expressed in hippocampal neurons7, 15, 38, we examined the subcellular distribution of GIRK2a and GIRK2c expressed in cultured hippocampal pyramidal neurons from mice lacking both GIRK2 and GIRK3 (Girk2 −/− /Girk3 −/− mice). The labeling patterns for GIRK2a and GIRK2c in neurons from Girk2 −/− /Girk3 −/− mice were comparable to those seen in Girk2 −/− neurons (Supplementary Fig. S3), indicating that the GIRK2 isoform-dependent difference in subcellular distribution is not dependent on GIRK3.
