The Journal of Neuroscience, February 15, 2001, 21(4):1087-1095
Differential Frequency-Dependent Regulation of Transmitter
Release by Endogenous Nitric Oxide at the Amphibian Neuromuscular
Synapse
Sébastien
Thomas and
Richard
Robitaille
Centre de Recherche en Sciences Neurologiques and Département
de physiologie, Université de Montréal, Montréal,
Québec, Canada H3C 3J7
Nitric oxide (NO) is a potent neuromodulator in the CNS and
PNS. At the frog neuromuscular junction (nmj), exogenous application of
NO reduces neurotransmitter release, and NO synthases (NOSs), the
enzymes producing NO, are present at this synapse. This work aimed at
studying the molecular mechanisms by which NO modulates synaptic
efficacy at the nmj using electrophysiological recordings and
Ca2+-imaging techniques. Bath application of the NO
donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside decreased end plate potential (EPP) amplitude as well as the frequency of miniature EPPs but not
their amplitude. Ca2+ responses elicited in
presynaptic terminals by single action potentials were unaffected by
NO, but responses evoked by a short train of stimuli were increased.
Tonic endogenous production of NO was observed as suggested by the
increase in EPP amplitude by bath application of the NO scavenger
hemoglobin and the neuronal NOS inhibitor 3-bromo-7-nitroindazole
sodium salt. A soluble guanylate cyclase inhibitor,
6-anilino-5,8-quinolinedione (LY-83583), increased EPP amplitude and
occluded the effects of the NO donor, suggesting that NO acts via a
cGMP-dependent mechanism. High-frequency-induced depression was reduced
in the presence of the NO scavenger but not by LY-83583. However,
adenosine-induced depression was significantly reduced after bath
perfusion of SNAP and in the presence of LY-83583. Our results indicate
that NO regulates transmitter release and adenosine-induced depression
via a cGMP-dependent mechanism that occurs after
Ca2+ entry and that high-frequency-induced synaptic
depression is regulated by NO in a cGMP-independent manner.
Key words:
nitric oxide; guanylate cyclase; adenosine; transmitter
release; synaptic depression; calcium; perisynaptic Schwann cells
Copyright © 2001 Society for Neuroscience 0270-6474/01/2141087-09$05.00/0
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