Effects and Mechanisms of Action of Nitric Oxide on Transmitter Release in Mouse Motor Nerve Terminals

Valiullina, Fliza; Ситдикова, Г. Ф.

doi:10.1007/s11062-012-9324-7

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…It is known that in neurons, glutamate, acting on post-synaptic NMDA receptors can induce NO release as nitric oxide synthase is a part of the NMDA/NOS complex (Courtney et al, 2014 ). Consistent with this, HCY neurotoxicity could be due to the release of NO (Stamler et al, 1993 ) which is a potent inhibitor of ACh release from motor nerve endings (Giniatullin et al, 2005 ; Valiullina and Sitdikova, 2012 ). Early studies indicate that the activation of muscle NMDA receptors by bath-applied glutamate increases synthesis of NO in muscle fibers and NO acts in a retrograde manner on motor nerve terminals to inhibit non-quantal release of ACh (Malomouzh et al, 2003 ).…”

Section: Discussionmentioning

confidence: 83%

Homocysteine aggravates ROS-induced depression of transmitter release from motor nerve terminals: potential mechanism of peripheral impairment in motor neuron diseases associated with hyperhomocysteinemia

Bukharaeva

Shakirzyanova

Khuzakhmetova

et al. 2015

Front. Cell. Neurosci.

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Homocysteine (HCY) is a pro-inflammatory sulphur-containing redox active endogenous amino acid, which concentration increases in neurodegenerative disorders including amyotrophic lateral sclerosis (ALS). A widely held view suggests that HCY could contribute to neurodegeneration via promotion of oxidative stress. However, the action of HCY on motor nerve terminals has not been investigated so far. We previously reported that oxidative stress inhibited synaptic transmission at the neuromuscular junction, targeting primarily the motor nerve terminals. In the current study, we investigated the effect of HCY on oxidative stress-induced impairment of transmitter release at the mouse diaphragm muscle. The mild oxidant H2O2 decreased the intensity of spontaneous quantum release from nerve terminals (measured as the frequency of miniature endplate potentials, MEPPs) without changes in the amplitude of MEPPs, indicating a presynaptic effect. Pre-treatment with HCY for 2 h only slightly affected both amplitude and frequency of MEPPs but increased the inhibitory potency of H2O2 almost two fold. As HCY can activate certain subtypes of glutamate N-methyl D-aspartate (NMDA) receptors we tested the role of NMDA receptors in the sensitizing action of HCY. Remarkably, the selective blocker of NMDA receptors, AP-5 completely removed the sensitizing effect of HCY on the H2O2-induced presynaptic depressant effect. Thus, at the mammalian neuromuscular junction HCY largely increases the inhibitory effect of oxidative stress on transmitter release, via NMDA receptors activation. This combined effect of HCY and local oxidative stress can specifically contribute to the damage of presynaptic terminals in neurodegenerative motoneuron diseases, including ALS.

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