differently from GluA1, in that essentially all native AMPARs in CA1 pyramidal neurons contain the GluA2 subunit (Lu et al., 2009)? We therefore examined the effect of CNIH-2 on GluA2 homomers in HEK cells. Unedited GluA2(Q) was used owing to its ability to form functional channels at higher levels than GluA2(R). Like GluA1 we found that CNIH-2 slowed deactivation of GluA2 homomers (Figures 6B). However, in sharp contrast to GluA1, the co-expression of γ-8 reversed the slowing of homomeric GluA2 kinetics caused by CNIH-2 (Figure 6B). The IKA/IGlu ratio of GluA2(Q) in the presence of both γ-8 and CNIH-2 was 0.48 ± 0.04 (n = 6), indicating a 4 γ-8 receptor (Figure S7). We repeated the experiments with GluA1A2(R) heteromers, the subunit composition that accounts for the majority of endogenous AMPARs in CA1 neurons (Lu et al., 2009). When GluA1A2 heteromers were co-expressed with either γ-8 or CNIH-2, CNIH-2 produced a much stronger slowing of deactivation compared to γ-8, as expected. Remarkably, however, co-expression of γ-8 and CNIH-2 with GluA1A2 heteromers reversed CNIH-2-induced slowing (Figure 6C). Together these findings are of considerable interest for two main reasons. One, such data are consistent with a model in which γ-8 prevents the
