The well-characterized laminar arrangement of the cell bodies of CA1 pyramidal cells in the adult hippocampus allowed us to investigate changes in the density of GIRK expression in dendritic spines as a function of distance from the soma in the adult. Quantitative comparison of immunogold densities showed that GIRK1 and GIRK2 followed a similar proximal-to-distal gradient in the hippocampal pyramidal cells, but GIRK3 did not show such a gradient. These differential expression patterns may contribute significantly to changes that determine the properties of GIRK channels and thereby influence different hippocampal function. Indeed, our data are consistent with previous electrophysiological studies showing that, in CA1 neurons from GIRK3 knockout mice, no differences in baclofen-evoked current relative to wild-type were observed (Koyrakh et al., 2005). Thus, GIRK3-containing channels seem to play only a modest role in the postsynaptic inhibitory effects of GABAB receptor stimulation (Koyrakh et al., 2005). In addition, the strikingly similar extrasynaptic distribution of GIRK1 and GIRK2 is reminiscent of the distribution of the GABAB receptor (Koyrakh et al., 2005; López-Bendito et al., 2004). Therefore, given our data, it seems reasonable to suggest that GIRK channels consisting of GIRK1 and GIRK2 mediate the dominant component of the GABAB-mediated postsynaptic inhibition.
