Functional diversify and developmental changes in rat neuronal kainate receptors

1. Whole-cell currents evoked by kainate and the GluR5-selective agonist (R X)-2-amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl)propanoic acid (ATPA) were used to compare the physiological properties of kainate receptors expresse d by neurons from rat hippocampus, spinal cord and dorsal root ganglia. 2. In contrast to kainate, which evoked desensitizing currents with similar decay rates and steady-state components in all three cell types, responses to ATPA were distinctly different in the three cell populations. Currents evoked by ATPA displayed a significant steady-state component in hippocampa l neurons, but decayed rapidly to baseline in dorsal root ganglion (DRG) ce lls. ATPA failed to evoke current in many of the spinal neurons. 3. ATPA caused steady-state desensitization in DRG cells with an IC50 of 41 nM. Recovery from desensitization of DRG cell receptors by ATPB was signif icantly slower than for any previously described agonist. In contrast, hipp ocampal kainate receptors recovered from desensitization by ATPA within a f ew seconds. 4. Half-maximal activation of kainate receptors in hippocampal neurons requ ired 938 nM ATPA. In DRG cells treated with concanavalin B the EC50 for ATP B was 341 nar. ATPA evoked current in embryonic hippocampal neurons but wit h lower amplitude relative to kainate than in cultured postnatal neurons. 5. Collectively, these results highlight functional differences between neu ronal kainate receptors that may reflect their distinct subunit composition and their diverse roles in synaptic transmission.