Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism

Neuron. 2001 Nov 8;32(3):477-88. doi: 10.1016/s0896-6273(01)00479-2.

Abstract

In the spinal cord dorsal horn, excitatory sensory fibers terminate adjacent to interneuron terminals. Here, we show that kainate (KA) receptor activation triggered action potential-independent release of GABA and glycine from dorsal horn interneurons. This release was transient, because KA receptors desensitized, and it required Na+ entry and Ca2+ channel activation. KA modulated evoked inhibitory transmission in a dose-dependent, biphasic manner, with suppression being more prominent. In recordings from isolated neuron pairs, this suppression required GABA(B) receptor activation, suggesting that KA-triggered GABA release activated presynaptic GABA(B) autoreceptors. Finally, glutamate released from sensory fibers caused a KA and GABA(B) receptor-dependent suppression of inhibitory transmission in spinal slices. Thus, we show how presynaptic KA receptors are linked to changes in GABA/glycine release and highlight a novel role for these receptors in regulating sensory transmission.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology
  • Glycine / metabolism*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Kainic Acid / pharmacology
  • Male
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Rats
  • Receptors, Kainic Acid / physiology*
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Excitatory Amino Acid Agonists
  • Receptors, Kainic Acid
  • gamma-Aminobutyric Acid
  • Kainic Acid
  • Glycine