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The Journal of Neuroscience, July 1, 2001, 21(13):4572-4581
Kainate Receptors Expressed by a Subpopulation of Developing
Nociceptors Rapidly Switch from High to Low Ca2+
Permeability
C. Justin
Lee1,
Haeyoung
Kong4,
M. Chiara
Manzini2, 3,
Cristóvão
Albuquerque1,
Moses V.
Chao4, and
Amy B.
MacDermott1, 3
1 Department of Physiology and Cellular Biophysics,
2 Department of Pathology, and the 3 Center for
Neurobiology and Behavior, Columbia University, New York, New York
10032, and 4 Molecular Neurobiology Program, Skirball
Institute, New York University Medical Center, New York, New
York 10016
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 (Bernard et al., 1999). 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.
Key words:
dorsal root ganglion; nociceptor; kainate receptor; calcium permeability; capsaicin; LD2; LA4; IB4; lamina II; C-fiber
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134572-10$05.00/0
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