TARP-associated AMPA receptors display an increased maximum channel conductance and multiple kinetically distinct open states

J Physiol. 2012 Nov 15;590(22):5723-38. doi: 10.1113/jphysiol.2012.238006. Epub 2012 Sep 17.


Fast excitatory synaptic transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs), whose biophysical properties are dramatically modulated by the presence of transmembrane AMPAR regulatory proteins (TARPs). To help construct a kinetic model that will realistically describe native AMPAR/TARP function, we have examined the single-channel properties of homomeric GluA1 AMPARs in combination with the TARPs, γ-2, γ-4 and γ-5. In a saturating concentration of agonist, each of these AMPAR/TARP combinations gave rise to single-channel currents with multiple conductance levels that appeared intrinsic to the receptor-channel complex, and showed long-lived subconductance states. The open time and burst length distributions of the receptor complexes displayed multiple dwell-time components. In the case of γ-2- and γ-4-associated receptors, these distributions included a long-lived component lasting tens of milliseconds that was absent from both GluA1 alone and γ-5-associated receptors. The open time distributions for each conductance level required two dwell-time components, indicating that at each conductance level the channel occupies a minimum of two kinetically distinct open states. We have explored how these data place novel constraints on possible kinetic models of TARP-associated AMPARs that may be used to define AMPAR-mediated synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / metabolism*
  • Cell Line
  • Humans
  • Ion Channel Gating*
  • Kinetics
  • Protein Multimerization
  • Rats
  • Receptors, AMPA / metabolism*


  • Cacng2 protein, rat
  • Cacng4 protein, rat
  • Cacng5 protein, rat
  • Calcium Channels
  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 1