While GIRK2a and GIRK2c exhibited comparable labeling patterns when expressed in cultured rat hippocampal neurons22, endogenous GIRK2 might mask isoform-dependent differences in the trafficking and/or function of exogenously expressed subunits. Thus, we sought to examine the subcellular distribution of each isoform when expressed individually in cultured hippocampal neurons from Girk2 −/− mice. AAV vectors harboring coding sequence for GIRK2a or GIRK2c, inserted downstream of the CaMKIIα promoter, were used to drive expression of untagged GIRK2a or GIRK2c (and EGFP, bi-cistronically) in Girk2 −/− neurons. Strong overlap between recombinant GIRK2 and endogenous CaMKIIα immunolabeling was observed (Supplementary Fig. S2), confirming that the expression of GIRK2 was restricted primarily to pyramidal neurons.
