Activation of AMPA receptors

Activation of AMPA receptors AMPA receptors are functionally either Ca permeable or Ca impermeable based on the subunit composition. Ca permeability is determined by GluR2 subunit which undergoes post-transcriptional RNA editing that changes glutamine (Q) at the pore to arginine (R). Incorporation of even a single subunit in the AMPA receptor confers Ca-limiting properties. Ca permeable AMPA receptors permit Ca and Na whereas Ca impermeable AMPA receptors permit only Na. In general, glutamatergic neurons contain Ca impermeable AMPA receptors and GABAergic interneurons contain Ca permeable AMPA receptors. However, some synapses do contain a mixture of Ca permeable and Ca impermeable AMPA receptors. GluR1-4 are encoded by four genes however, alternative splicing generates several functional subunits namely long and short forms of GluR1 and GluR2. GluR4 has long tail only and GluR3 has short tail only. Besides the differences in the tail length, flip/flop isoforms are generated by an interchangeable exon that codes the fourth membranous domain towards the C terminus. The fip/flop isoforms determine rate of desensitization/resensitization and the rate of channel closing. Receptors homomers or heteromers assembled from the combination of GluR1-4 subunits that vary in C tail length and flip/flop versions generates a whole battery of functionally distinct AMPA receptors.