The fast kinetics of AMPA GluR3 receptors is selectively modulated by the TARPs γ4 and γ8

Transmembrane AMPA receptor-associated regulatory proteins (TARPs) modulate the kinetics of AMPA receptors and increase their surface expression. This study compared the effects of the TARPs γ2, γ3, γ4 and γ8 on the AMPA receptor subunits GluR1–3. We found that the deactivation and desensitization time constants of GluR3 receptors were greatly increased by γ4 and γ8 (∼ 3 fold) whereas γ2 and γ3 caused minimal changes. This stands in contrast to the effects on GluR1 and GluR2 receptors which were similar across all four TARPs. Other response parameters like the current density, the EC50 for glutamate-induced peak currents, and kainate-induced currents were in general more effectively modulated by γ2 and γ3 in all subunits, including GluR3. All TARPs were effective in increasing the unitary conductance. The differential TARP effects on deactivation time constants of the GluR3 subunit are likely to have a significant impact on synaptic responses across different neurons in the brain.