We next asked whether GIRK2a and GIRK2c conferred unique functionality to GIRK channels in cultured hippocampal pyramidal neurons. Whole-cell currents evoked by GABABR stimulation were measured in wild-type and Girk2 −/− pyramidal neurons expressing EGFP, and in Girk2 −/− pyramidal neurons expressing GIRK2a or GIRK2c. Baclofen evoked a prominent inward current in wild-type pyramidal neurons that was not seen in Girk2 −/− control neurons expressing EGFP alone (Fig. 5A,B). Viral expression of either GIRK2 isoform in Girk2 −/− pyramidal neurons yielded baclofen-induced currents that were larger than currents in wild-type controls. Activation (but not deactivation) kinetics of the baclofen-induced currents in Girk2 −/− pyramidal neurons expressing GIRK2a or GIRK2c also differed from those in wild-type control neurons, though no isoform-dependent differences were found (Fig. 5C,D). Similarly, while there was no isoform-dependent difference in channel sensitivity (EC50) to GABABR activation, GABABR-GIRK coupling efficiency in both cases was diminished relative to wild-type controls (Fig. 5E).
