FUNCTIONAL KAINATE-SELECTIVE GLUTAMATE RECEPTORS IN CULTURED HIPPOCAMPAL-NEURONS

Glutamate mediates fast synaptic transmission at the majority of excit atory synapses throughout the central nervous system by interacting wi th different types of receptor channels. Cloning of glutamate receptor s has provided evidence for the existence of several structurally rela ted subunit families, each composed of several members. It has been pr oposed that KA1 and KA2 and GluR-5, GluR-6, and GluR-7 families repres ent subunit classes of high-affinity kainate receptors and that in viv o different kainate receptor subtypes might be constructed from these subunits in heteromeric assembly. However, despite some indications fr om autoradiographic studies and binding data in brain membranes, no fu nctional pure kainate receptors have so far been detected in brain cel ls. We have found that early after culturing, a high percentage of rat hippocampal neurons express functional, kainate-selective glutamate r eceptors. These kainate receptors show pronounced desensitization with fast onset and very slow recovery and are also activated by quisquala te and domoate, but not by a-amino-3-hydroxy-5-methylisoxazole-4-propi onate. Our results provide evidence for the existence of functional gl utamate receptors of the kainate type in nerve cells, which are likely to be native homomeric GluR-6 receptors.