Characterizing the site and mode of action of dynorphin at hippocampal mossy fiber synapses in the guinea pig

Pablo E. Castillo, Paul A. Salin, Marc G. Weisskopf, Roger A. Nicoll

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Extracellular field potential recordings from the CA3 region in guinea pig hippocampal slices were used to study the release and action of dynorphin at the mossy fiber synapse. Dynorphin A(1-17) or U69593 inhibited mossy fiber synaptic responses in preparations in which the CA3 region was surgically isolated from the rest of the hippocampus. This inhibition was completely reversed by the κ1 selective antagonist nor-BNI, thus establishing the presence of functional κ1 receptors in CA3. Inhibitory effects of dynorphin on mossy fiber responses were unaltered in the presence of the N- or P-type Ca2+ channel blockers, ω-CgTx or ω-Aga IVA, respectively. This indicates that the action of dynorphin is independent of the particular type of Ca2+ channel that mediates transmitter release at the mossy fiber terminal. Heterosynaptic inhibition of mossy fiber responses was observed in the presence of nifedipine, ω-CgTx, or ω-Aga IVA, indicating that dynorphin release does not depend specifically on L-, N-, or P-type Ca2+ channels. The blockade of heterosynaptic inhibition by the membrane-permeant Ca2+ chelator EGTA-AM suggests the involvement of a slow Ca2+-dependent process in dynorphin release. On the basis of a variety of experimental evidence, we propose that the time course of heterosynaptic inhibition is determined primarily by the time course of clearance of dynorphin in the extracellular space.

Original languageEnglish (US)
Pages (from-to)5942-5950
Number of pages9
JournalJournal of Neuroscience
Volume16
Issue number19
StatePublished - Oct 1 1996
Externally publishedYes

Fingerprint

Hippocampal Mossy Fibers
Dynorphins
Synapses
Guinea Pigs
Extracellular Space
Nifedipine
Chelating Agents
Hippocampus
Membranes

Keywords

  • κ receptors
  • calcium channels
  • dynorphin
  • hippocampus
  • mossy fibers
  • opioid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Characterizing the site and mode of action of dynorphin at hippocampal mossy fiber synapses in the guinea pig. / Castillo, Pablo E.; Salin, Paul A.; Weisskopf, Marc G.; Nicoll, Roger A.

In: Journal of Neuroscience, Vol. 16, No. 19, 01.10.1996, p. 5942-5950.

Research output: Contribution to journalArticle

Castillo, Pablo E. ; Salin, Paul A. ; Weisskopf, Marc G. ; Nicoll, Roger A. / Characterizing the site and mode of action of dynorphin at hippocampal mossy fiber synapses in the guinea pig. In: Journal of Neuroscience. 1996 ; Vol. 16, No. 19. pp. 5942-5950.
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