Dual Effects of TARP γ-2 on Glutamate Efficacy Can Account for AMPA Receptor Autoinactivation

Cell Rep. 2017 Aug 1;20(5):1123-1135. doi: 10.1016/j.celrep.2017.07.014.


Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs) associated with transmembrane AMPAR regulatory proteins (TARPs). At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy. Simulations show that, by shifting the balance between AMPAR activation and desensitization, TARPs can markedly facilitate the transduction of spillover-mediated synaptic signaling. Furthermore, the dual effects of TARPs can account for biphasic steady-state glutamate concentration-response curves-a phenomenon termed "autoinactivation," previously thought to reflect desensitization-mediated AMPAR/TARP dissociation.

Keywords: EPSC; GluA1; cerebellar granule cell; diffusion model; kinetic model; short-term plasticity; single-channel; spillover; subconductance; synaptic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism*
  • HEK293 Cells
  • Humans
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*


  • CACNG2 protein, human
  • Calcium Channels
  • Receptors, AMPA
  • Glutamic Acid