%0 Journal Article %A Sébastien Thomas %A Richard Robitaille %T Differential Frequency-Dependent Regulation of Transmitter Release by Endogenous Nitric Oxide at the Amphibian Neuromuscular Synapse %D 2001 %R 10.1523/JNEUROSCI.21-04-01087.2001 %J The Journal of Neuroscience %P 1087-1095 %V 21 %N 4 %X 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. %U https://www.jneurosci.org/content/jneuro/21/4/1087.full.pdf