Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition.
Non-NMDA glutamate receptor subunits of the AMPA-preferring subfamily combine to form ion channels with heterogeneous functional properties. We have investigated the effects of RNA editing at the Q/R site, splice variation of the "flip/flop" cassette, and multimeric subunit assembly on the single-channel conductance and kinetic properties of the recombinant AMPA receptors formed from GluR2 and GluR4 expressed in HEK 293 cells. We found that AMPA receptor single-channel conductance was dependent on the Q/R site editing state of the subunits comprising the channel. Calcium-permeable (unedited) channels had resolvable single-channel events with main conductance states of 7-8 pS, whereas fully edited GluR2 channels had very low conductances of approximately 300 fS (estimated from noise analysis). Additionally, the flip splice variant of GluR4 conferred agonist-dependent conductance properties reminiscent of those found for a subset of AMPA receptors in cultured cerebellar granule cells. These results provide a description of the single-channel properties of certain recombinant AMPA receptors and suggest that the single-channel conductance may be determined by the expression of edited GluR2 subunits in neurons.
Swanson
G T
GT
Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom.
Kamboj
S K
SK
Cull-Candy
S G
SG
D002460:Cell Line; D004553:Electric Conductivity; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D007700:Kinetics; D017393:RNA Editing; D012326:RNA Splicing; D018091:Receptors, AMPA / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins
D007473:Ion Channels; D018091:Receptors, AMPA; D011994:Recombinant Proteins