The impact of alternative splicing of the Girk2 (Kcnj6) gene on GIRK channel trafficking and function is unclear. GIRK2c (but not GIRK2a) was reported to bind PSD-95 in one study31, but not in others32, 33. GIRK2c (but not GIRK2a) was also reported to bind to SAP-97, and co-expression of SAP-97 with GIRK2c conferred both basal activity and G protein-dependent gating to GIRK2c homomeric channels expressed in Xenopus oocytes34. To date, however, the attributes of GIRK2a and GIRK2c have not been systematically compared in mammalian cell systems. In this study, we expressed GIRK2a and GIRK2c independently in neurons lacking GIRK2, and compared their subcellular distributions and respective abilities to rescue GIRK channel function and GIRK-dependent behavior.
