Kainate receptor-mediated inhibition of glutamate release involves protein kinase A in the mouse hippocampus

J Neurophysiol. 2006 Oct;96(4):1829-37. doi: 10.1152/jn.00280.2006. Epub 2006 Jun 28.


The mechanisms involved in the inhibition of glutamate release mediated by the activation of presynaptic kainate receptors (KARs) at the hippocampal mossy fiber-CA3 synapse are not well understood. We have observed a long-lasting inhibition of CA3 evoked excitatory postsynaptic currents (eEPSCs) after a brief application of kainate (KA) at concentrations ranging from 0.3 to 10 muM. The inhibition outlasted the change in holding current caused by the activation of ionotropic KARs in CA3 pyramidal cells, indicating that this action is not contingent on the opening of the receptor channels. The inhibition of the eEPSCs by KA was prevented by G protein and protein kinase A (PKA) inhibitors and was enhanced after stimulation of the adenylyl cyclase (AC) with forskolin. We conclude that KARs present at mossy fiber terminals mediate the inhibition of glutamate release through a metabotropic mechanism that involves the activation of an AC-second messenger cAMP-PKA signaling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / drug effects
  • Adenylyl Cyclases / physiology
  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / physiology
  • GTP-Binding Proteins / physiology
  • Glutamic Acid / metabolism*
  • Hippocampus / metabolism*
  • Kainic Acid / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / physiology
  • Pyramidal Cells / physiology
  • Receptors, Kainic Acid / drug effects
  • Receptors, Kainic Acid / physiology*
  • Second Messenger Systems / physiology*
  • Signal Transduction / physiology


  • Receptors, Kainic Acid
  • Colforsin
  • Glutamic Acid
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Kainic Acid