Kainate Receptors Expressed by a Subpopulation of Developing Nociceptors Rapidly Switch from High to Low Ca2+Permeability

摘要

Dorsal root ganglion (DRG) neurons first express kainate receptor subunits, predominantly GluR5, during embryonic development. In the DRG and throughout the nervous system, substantial editing of GluR5 mRNA occurs with developmental maturation (). The accompanying change in Ca²⁺ permeability of functional kainate receptors that is the predicted outcome of this developmental regulation of mRNA editing has not been investigated. Here we report that kainate receptors on DRG neurons from late embryonic and newborn rats are predominantly Ca²⁺permeable but then become fully Ca²⁺ impermeable later in the first postnatal week. Using multiple markers for nociceptor subpopulations, we show that this switch in Ca²⁺ permeability is not caused by the appearance of a new subpopulation of nociceptors with different receptor properties. Instead, the change in Ca²⁺ permeability matches the time course of post-transcriptional RNA editing of GluR5 at the Q/R site within the pore of the channel, indicating that the change is probably caused by developmentally regulated RNA editing. We also report that, on the basis of the strong correlation of receptor expression with expression of the surface markers LA4, isolectin B4, and LD2, kainate receptors are present on C-fiber-type neurons projecting to lamina II of spinal cord dorsal horn. These results raise the possibility that kainate receptors in their Ca²⁺-permeable form serve a developmental role in synapse formation between this population of C-fibers and their targets in the spinal cord dorsal horn. Thereafter, the receptors may serve a new function that does not require Ca²⁺permeability.