Kainate receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn

Geoffrey A. Kerchner, Timothy J. Wilding, James E. Huettner, Min Zhuo

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

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, G/uR5 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.

Original languageEnglish
Pages (from-to)8010-8017
Number of pages8
JournalJournal of Neuroscience
Volume22
Issue number18
DOIs
StatePublished - Sep 15 2002

Keywords

  • Dorsal horn
  • Dorsal root ganglion
  • GluR5
  • GluR6
  • Glutamate receptor
  • Kainate
  • Presynaptic
  • Sensory transmission
  • Spinal cord

Fingerprint Dive into the research topics of 'Kainate receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn'. Together they form a unique fingerprint.

Cite this