Independent regulation of kinetic properties in human recombinant GluR subunit coassemblies

AMPA-type receptor (AMPAR) channels are the most abundant excitatory ligand-gated receptor channels of the vertebrate central nervous system for fast synaptic transmission.

Four subunits with different posttranscriptional modifications and splice variants are known. In vivo they occur as tetrameric heteromeric receptors. Posttransscriptional editing of this subunits at the Q/R-site controls calcium permeability and receptor rectification whereas editing at the R/G-site and alternative splicing are involved in the regulation of biophysical properties.

We used patch-clamp techniques with ultrafast solution exchange to examine the kinetics of recombinant human homomeric and heteromeric AMPA-type-receptor channels transiently expressed in HEK293 cells. In the present study we analyzed the time course of desensitization, resensitization and the I/V-dependancy of different homomeric and heteromeric GluR channels.

Homomeric or hetromeric expression of the edited GluR2-subunit (R) (edited at Q/R-site) showed a strong linear I/V-dependancy whereas coassemblies with non-edited subunits (Q) showed receptor rectification. We found that the desensitization had intermediate values depending on the amount of cDNA of the respective subunit at all heteromeric and homomeric GluR channels tested. The same holds true for the resensitization except GluR2 flip channels were coexpressed with GluR1 channels. In this case, the resensitization had values close to that of the fast resensitising GluR2 flip channels, even in case of abundance of cDNAs of other subunits in cotransfection experiments.

In conclusion, the GluR2 flip subunit that is regulated specifically during embryonic development and also in case of neurodegenerative disorders, determines the resensitization kinetics of AMPAergic channels and thus controls the following frequency and calcium-influx at AMPAergic synapses.