HEK cells may lack factors that support GIRK2 isoform-specific contributions to channel trafficking and function, and thus, we next sought to compare the GIRK2 variants in a cell type in which they are normally expressed. Cell biological, biochemical, and electrophysiological studies involving wild-type and Girk2 −/− mice have confirmed the presence of GIRK2 in mouse hippocampal neurons10, 15. Using RNA-Seq and laser-captured tissue samples from the adult mouse, we probed for Girk2a and Girk2c mRNAs in the CA1 region of the hippocampus. Because the 3′-UTR regions of Girk2a and Girk2c mRNAs are distinct and may influence their subcellular trafficking29, we compared transcript levels in cell body (stratum pyramidale) and neuropil (stratum radiatum) samples. Both transcripts were detected in neuropil, albeit at significantly lower levels than seen in CA1 cell body samples (q = 0.0012 for Girk2a and 0.0125 for Girk2c), suggesting that an active RNA trafficking mechanism exists for both isoforms (Fig. 2A). Higher levels of Girk2c mRNA relative to Girk2a mRNA were detected, with the difference reaching statistical significance in neuropil (P = 0.04) but not cell bodies (P
