The Journal of Neuroscience, September 15, 2002, 22(18):8010-8017
Kainate Receptor Subunits Underlying Presynaptic Regulation of
Transmitter Release in the Dorsal Horn
Geoffrey A.
Kerchner1,
Timothy J.
Wilding2,
James
E.
Huettner2, and
Min
Zhuo1
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
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 mice deficient in the KA
receptor subunit were used to evaluate the contributions 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. 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.
Key words:
kainate; glutamate receptor; presynaptic; GluR5; GluR6; spinal cord; dorsal horn; dorsal root ganglion; sensory
transmission
Copyright © 2002 Society for Neuroscience 0270-6474/02/22188010-08$05.00/0
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