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 perhaps diminish the relevance of arguments concerning the presence of CNIH proteins on surface AMPARs. However, we do detect the expression of endogenous CNIH on the surface of neurons and are able to observe effects of CNIH-2 on synaptic AMPAR gating in the absence of γ-8. Therefore it is possible for CNIH proteins to associate with synaptic AMPARs. As stated above, such data point to a selective and potentially inert association of CNIH proteins with GluA1 subunits of synaptic GluA1A2 heteromers, with γ-8 bound to all four subunits, as previously proposed (Shi et al., 2009).
