SINGLE-CHANNEL PROPERTIES OF RECOMBINANT AMPA RECEPTORS DEPEND ON RNAEDITING, 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, spli ce variation of the ''flip/flop'' cassette, and multimeric subunit ass embly on the single-channel conductance and kinetic properties of the recombinant AMPA receptors formed from GluR2 and GluR4 expressed in HE K 293 cells. We found that AMPA receptor single-channel conductance wa s dependent on the Q/R site editing state of the subunits comprising t he channel. Calcium-permeable (unedited) channels had resolvable singl e-channel events with main conductance states of 7-8 pS, whereas fully edited GluR2 channels had very low conductances of similar to 300 fS (estimated from noise analysis). Additionally, the flip splice variant of GluR4 conferred agonist-dependent conductance properties reminisce nt of those found for a subset of AMPA receptors in cultured cerebella r granule cells. These results provide a description of the single-cha nnel 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.