The marked slowing of deactivation is one of the most prominent effects of CNIH-2 on heterologously expressed AMPARs. Does CNIH-2 make any contribution to the kinetics of AMPARs in CA1 pyramidal neurons? As discussed above, the speeding of AMPAR kinetics in neurons lacking CNIH-2/-3 can be fully accounted for by the selective loss of GluA1-containing receptors without any need for a direct action of CNIH-2 on the gating of surface/synaptic AMPARs, raising the question as to whether CNIH-2 is, in fact, associated with surface/synaptic AMPARs. Results from other groups (Gill et al., 2011; Kato et al., 2010a), based largely on data from heterologous cells, found that CNIH proteins prevent AMPAR resensitization, suggesting that the lack of resensitization in neurons is due to the presence of CNIH proteins. However, we failed to see resensitization in neurons lacking CNIH proteins (Figure S3C). We also found that γ-8 reverses the effects of CNIH-2 on the deactivation of GluA1A2 heteromers. Taken together these findings may leave very little room for a physiologically relevant role for CNIH proteins on synaptic AMPAR gating in neurons and
