The fast kinetics seen with this heteromer in the presence of γ-8 and CNIH in HEK cells indicates that CNIH has little effect suggesting the absence of CNIH on this heteromer on the surface (Figure 6C). Alternatively, because CNIH does interact with surface GluA1 homomers in the presence of γ-8 (Figure 6A), CNIH could be associated with GluA1 subunits of surface GluA1A2 heteromers but not affect the kinetics of these heteromers. Wild-type AMPARs in CA1 pyramidal neurons are primarily GluA1A2 (Lu et al., 2009) and exhibit deactivation kinetics characteristic of limited CNIH influence on GluA1A2 gating kinetics (Figure 4D and 6C). In the hippocampus our biochemical data show that CNIH-2 associates exclusively with GluA1A2 receptors through the GluA1 subunit (Figure 3I and S8B), and we do observe CNIH-2 on the surface of hippocampal neurons (Figure 5G). Because of such data we would argue that native surface GluA1A2 receptors could have up to 2 CNIH associated with the GluA1 subunits, but that, if present, they exert no effect on gating kinetics due to γ-8’s prevention of a functional CNIH association with
