Av. Paternain et al., GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors, J NEUROSC, 20(1), 2000, pp. 196-205
We have performed nonradioactive double in situ hybridization to study the
expression of glutamic acid decarboxylase and GluR6 or GluR5 subunits in hi
ppocampal slices. Our results indicate that although GluR6 is primarily exp
ressed by pyramidal cells and dentate granule neurons and GluR5 is prominen
tly expressed in nonpyramidal cells, there is a significant population of G
ABAergic interneurons that coexpress the two glutamate receptor subunits. T
o assess whether the two subunits could coassemble to form heteromeric rece
ptors, we studied the electrophysiological responses when both subunits wer
e coexpressed in HEK293 cells. Responses evoked by rapid application of eit
her glutamate, (RS)-alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionic
acid (ATPA) the selective agonist of GluR5 receptors), and AMPA in cells co
transfected with GluR6(R) and GluR5(Q) presented a similar degree of outwar
d rectification. This can only be attributed to the fact that all receptors
have at least one GluR6(R) subunit in their structure, conferring outward
rectification, and at least one GluR5(Q) subunit to confer sensitivity to A
TPA and AMPA. More than 80% of the receptors expressed by a single cell wer
e found to be GluR5/R6 heteromers, presenting different desensitization and
gating properties to homomeric R6 receptors. These results lead us to beli
eve that a population of interneurons in the hippocampus express receptors
made up of both GluR5 and GluR6 subunits and provide evidence for a greater
diversity of kainate receptors in the brain than previously thought, that
may account for a higher functional complexity.