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Volume 16, Number 19,
Issue of October 1, 1996
pp. 5942-5950
Copyright ©1996 Society for Neuroscience
Characterizing the Site and Mode of Action of Dynorphin at
Hippocampal Mossy Fiber Synapses in the Guinea Pig
Received March 15, 1996; revised July 2, 1996; accepted July 8, 1996.
Pablo E. Castillo,
Paul A. Salin,
Marc G. Weisskopf, and
Roger A. Nicoll
Departments of Cellular and Molecular Pharmacology and Physiology,
University of California at San Francisco, San Francisco, California
94143-0450
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 1
selective antagonist nor-BNI, thus establishing the presence of
functional 1 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, -CgTx or -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, -CgTx, or -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.
Key words:
dynorphin;
receptors;
calcium channels;
hippocampus;
mossy fibers;
opioid
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