One important finding emerging from our data is that GIRK channel subunits are also regulated at synaptic sites during development. Indeed, we show here that excitatory PSDs exhibit profound changes in relative protein composition and abundance of GIRK2 during development. In contrast, the GIRK1 subunit was never detected at synaptic sites and the GIRK3 subunit levels were constant throughout postnatal development. The absence of GIRK1 in the postsynaptic specialization during development and adulthood is additional evidence of the molecular diversity of GIRK channels in the central nervous system and is consistent with observations in other brain regions (Fernández-Alacid et al., 2009; Koyrakh et al., 2005; Marker et al., 2005). Our data suggest that GIRK channels within the synaptic specialization are likely to be GIRK2/GIRK3 heterotetramers. This specific distribution of GIRK channels within the PSDs may reflect the presence of a PSD-95, Dlg and ZO-1 (PDZ) interaction motif on the GIRK2c splice isoform and/or GIRK3 (Inanobe et al., 1999; Nehring et al., 2000; Kurachi & Ishii, 2004). At present, the functional significance of GIRK channels within the synaptic specialization is unknown,
