Why is the action of CNIH-2/-3 confined to the GluA1 subunit? Previous studies in heterologous systems have shown that CNIH-2 has significant effects on AMPARs containing and lacking GluA1 subunits (Schwenk et al., 2009). To address this seeming contradiction, we examined the interactions between CNIH-2 and γ-8, the most prevalent TARP in the hippocampus (Rouach et al., 2005), on the kinetics of AMPARs of defined subunit composition. Remarkably, while γ-8 was incapable of reversing the slowing caused by CNIH-2 on homomeric GluA1 receptors, it fully reversed the slowing caused by CNIH-2 on homomeric GluA2 receptors, revealing exquisite selectivity of CNIH-2 for GluA1 over GluA2 due to γ-8 preventing a functional association of CNIH-2 with GluA2.
