γ-8 KO mice and found that CNIH-2 not only rescued the amplitude of the AMPAR-mEPSCs (Figure 7A), but also markedly slowed mEPSC responses, such that the kinetics were considerably slower than what is seen in wild-type neurons or when CNIH-2 is overexpressed in wild-type neurons (Figure 7B). These data are compelling for several reasons. One, they show that CNIH-2 effects on AMPAR kinetics are similar in HEK cells and in neurons lacking γ-8. Two, they emphasize the critical role that γ-8 has in determining the effects of CNIH-2/-3 on AMPAR kinetics. And three, they demonstrate that CNIH proteins are able to associate with synaptic AMPARs. While we maintain that the primary role for CNIH proteins is in the selective trafficking of GluA1A2 heteromers to synapses, the presence of CNIH protein on the surface of neurons (Figure 5G) and the ability CNIH-2 to influence gating properties of synaptic AMPARs in the absence of γ-8 (Figure 7B) are consistent with a selective and likely inert association of CNIH protein with GluA1 subunits of native synaptic GluA1A2 heteromers in the presence of γ-8.
