title: TARP-associated AMPA receptors display an increased maximum channel conductance and multiple kinetically distinct open states.
abstract: 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.
authors.affiliation: Department of Neuroscience, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Shelley
authors.forename: Mark
authors.initials: M
authors.lastname: Farrant
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Cull-Candy
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D055503:Protein Multimerization; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D018091:Receptors, AMPA; C491911:Cacng2 protein, rat; C522274:Cacng4 protein, rat; C532434:Cacng5 protein, rat