Given the association of GIRK channel subunits in the cerebellum and hippocampus (Aguado et al., 2008; Fernández-Alacid et al., 2009; Koyrakh et al., 2005), one might predict that, as in other hetero-oligomeric ion channels (Ball et al., 2010), the loss of a given subunit would affect the expression and/or turnover of other subunits. We addressed this issue in quantitative histoblotting experiments involving only adult GIRK2 null mice (Fig. 3). In the cerebellum, GIRK1 was reduced in both the molecular (11 ± 1%; p < 0.05) and granule cell (30 ± 2%; p < 0.05) layers. In the hippocampus, GIRK1 was lower in the CA1 (50 ± 4%, p < 0.05), CA3 (34 ± 3%, p < 0.05) and molecular layer of the DG (18 ± 1%; p < 0.05), but was normal in the hilus (Fig. 3A, C and E). GIRK1 levels were also lower in the caudate putamen (8 ± 1%, p < 0.05). Thus, we found that the GIRK1 subunit was consistently and significantly down-regulated in the GIRK2 null mice, although this regulation was different depending on the brain region and the layer or subfield of each region.
