In heterologous cells CNIH-2 has marked effects on GluA1-containing and lacking AMPARs (Schwenk et al., 2009). What then accounts for the selective effects of CNIH-2 deletion on native GluA1-containing receptors? Furthermore, how can one reconcile the fact that all CNIH binding sites appear to be occupied in CA1 neurons and yet endogenous AMPAR kinetics are considerably faster than the kinetics of AMPARs co-expressed with CNIH-2 in expression systems? To better understand the AMPAR kinetics in expression systems, we examined a variety of conditions. Initially, we measured the effects of CNIH-2 and γ-8, the primary TARP in the hippocampus (Rouach et al., 2005), on receptors of defined subunit composition in HEK cells. As seen previously, CNIH-2 significantly slowed deactivation of GluA1 homomeric receptors and to a greater extent than γ-8 (Figure 6Ai). Expression of both CNIH-2 and γ-8 did not significantly change the slowing seen with CNIH-2 alone (Figure 6Ai).
