Previous immunoelectron microscopy studies have shown that GIRK1 and GIRK2 labeling is concentrated at the peri- and extra-synaptic positions relative to the postsynaptic density (PSD) in hippocampal CA1. In addition, GIRK2 (but not GIRK1) labeling was detected within the PSD of CA1 pyramidal neurons15. The presence of a PDZ domain on the C-terminus of GIRK2c suggested that this isoform might promote the distribution of GIRK channels within or around the PSD, by virtue of its interaction with a scaffolding protein such as PSD-95. As noted above, GIRK2c was reported to bind PSD-9531, as well as SAP-9734. Moreover, SAP97 conferred both basal activity and G protein-dependent gating to GIRK2c-containing channels expressed in Xenopus oocytes34. Our data here, however, show that GIRK2a and GIRK2c assume comparable subcellular distributions relative to PSD-95 in mouse hippocampal pyramidal neurons. Thus, alternative splicing of the coding sequence of the Girk2 gene does not seem to influence the position of GIRK channels relative to the PSD. We did, however, detect significantly more Girk2c than Girk2a mRNA in the neuropil of CA1 in vivo, suggesting that RNA localization
