Postsynaptic production of nitric oxide implicated in long-term depression at the mature amphibian (Bufo marinus) neuromuscular junction

The Journal of Physiology
Sarah Jane Etherington, Alan William Everett

Abstract

We report here evidence for endogenous NO signalling in long-term (>1 h) synaptic depression at the neuromuscular junction induced by 20 min of 1 Hz nerve stimulation. Synaptic depression was characterized by a 46% reduction in the end-plate potential (EPP) amplitude and a 21% decrease in miniature EPP (MEPP) frequency, but no change to MEPP amplitude, indicating a reduction in evoked quantal release. Both the membrane-impermeant NO scavenger cPTIO and the NOS inhibitor L-NAME blocked depression, suggesting that it is induced by NO originating from a source outside the terminal. The depression was dependent on activation of muscle-type, but not neuronal-type, nAChRs and was still observed when Ca2+ release from the sarcoplasmic reticulum and muscle contraction were blocked with dantrolene. These data suggest that the depression depends on transmission, but not muscle contraction. The calcineurin inhibitors cyclosporin A and FK506, as well as ODQ, an inhibitor of NO-sensitive soluble guanylyl cyclase, Rp-8-pCPT-cGMPS, an inhibitor of cGMP-dependent protein kinase, and the calmodulin antagonist phenoxybenzamine also blocked depression. We propose that low frequency synaptic transmission leads to production of NO at the synapse an...Continue Reading

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Citations

Apr 26, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Haipeng ZhuChristopher M Gomez
Aug 30, 2014·Molecular and Cellular Neurosciences·Selwyn S JayakarJoseph F Margiotta
Apr 6, 2007·The European Journal of Neuroscience·Zachary NewmanClark Lindgren
Jul 1, 2008·The European Journal of Neuroscience·John Garthwaite
Aug 16, 2008·The European Journal of Neuroscience·Audrée Pinard, Richard Robitaille
Sep 28, 2016·Nature Neuroscience·Claire PiochonChristian Hansel
Sep 10, 2018·Biochemistry. Biokhimii︠a︡·E O TarasovaO P Balezina
Feb 8, 2020·Biochemical and Biophysical Research Communications·Andrei N TsentsevitskyIrina V Kovyazina

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