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The Journal of Neuroscience, January 1, 2001, 21(1):59-66
Presynaptic Kainate Receptors Regulate Spinal Sensory
Transmission
Geoffrey A.
Kerchner1,
Timothy J.
Wilding2,
Ping
Li1,
Min
Zhuo1, and
James E.
Huettner2
1 Washington University Pain Center and Departments of
Anesthesiology, Anatomy and Neurobiology, and Psychiatry, and
2 Department of Cell Biology and Physiology, Washington
University School of Medicine, St. Louis, Missouri 63110
Small diameter dorsal root ganglion (DRG) neurons, which include
cells that transmit nociceptive information into the spinal cord, are
known to express functional kainate receptors. It is well established
that exposure to kainate will depolarize C-fiber afferents arising from
these cells. Although the role of kainate receptors on sensory
afferents is unknown, it has been hypothesized that presynaptic kainate
receptors may regulate glutamate release in the spinal cord. Here
we show that kainate, applied at low micromolar concentrations in
the presence of the AMPA-selective antagonist
(RS)-4-(4-aminophenyl)-1,2-dihydro-1-methyl-2-propyl-carbamoyl-6,7-methylenedioxyphthalazine, suppressed spontaneous NMDA receptor-mediated EPSCs in cultures of
spinal dorsal horn neurons. In addition, kainate suppressed EPSCs in
dorsal horn neurons evoked by stimulation of synaptically coupled DRG
cells in DRG-dorsal horn neuron cocultures. Interestingly, although
the glutamate receptor subunit 5-selective kainate receptor agonist
(RS)-2- -amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) (2 µM) was able to suppress
DRG-dorsal horn synaptic transmission to a similar extent as kainate
(10 µM), it had no effect on excitatory transmission
between dorsal horn neurons. Agonist applications revealed a striking
difference between kainate receptors expressed by DRG and dorsal horn
neurons. Whereas DRG cell kainate receptors were sensitive to both
kainate and ATPA, most dorsal horn neurons responded only to kainate.
Finally, in recordings from dorsal horn neurons in spinal slices,
kainate and ATPA were able to suppress NMDA and AMPA receptor-mediated EPSCs evoked by dorsal root fiber stimulation. Together, these data
suggest that kainate receptor agonists, acting at a presynaptic locus,
can reduce glutamate release from primary afferent sensory synapses.
Key words:
kainate, presynaptic, ATPA, glutamate receptor subunit 5, glutamate, autoreceptor, excitatory synaptic transmission, NMDA
Copyright © 2001 Society for Neuroscience 0270-6474/01/21159-08$05.00/0
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