Kainate receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn.
Presynaptic kainate (KA) receptors regulate synaptic transmission at both excitatory and inhibitory synapses in the spinal cord dorsal horn. Previous work has demonstrated pharmacological differences between the KA receptors expressed by rat dorsal horn neurons and those expressed by the primary afferent sensory neurons that innervate the dorsal horn. Here, neurons isolated from KA receptor subunit-deficient mice were used to evaluate the contribution of glutamate receptor subunit 5 (GluR5) and GluR6 to the presynaptic control of transmitter release and to KA receptor-mediated whole-cell currents in these two cell populations [corrected]. Deletion of GluR6 produced a significant reduction in KA receptor-mediated current density in dorsal horn neurons, whereas GluR5 deletion caused no change in current density but removed sensitivity to GluR5-selective antagonists. Presynaptic modulation of inhibitory transmission between dorsal horn neurons was preserved in cells from either GluR5- or GluR6-deficient mice. In DRG neurons, in contrast, GluR5 deletion abolished KA receptor function, whereas deletion of GluR6 had little effect on peak current density but increased the rate and extent of desensitization. These results highlight fundamental differences in KA receptor physiology between the two cell types and suggest possible strategies for the pharmacological modulation of nociception.
Kerchner
Geoffrey A
GA
Washington University Pain Center and Departments of Anesthesiology, Anatomy and Neurobiology, and Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Wilding
Timothy J
TJ
Huettner
James E
JE
Zhuo
Min
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D021122:Protein Subunits; D018092:Kainic Acid Receptors / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D000097806:GluK2 Kainate Receptor
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor