Action of Hydrogen Peroxide on Synaptic Transmission at the Mouse Neuromuscular Junction

Abstract Hydrogen peroxide (H 2 O 2 ) is one of the reactive oxygen species (ROS), endogenously produced during metabolism, which acts as a second messenger. In skeletal muscles, hypoxia- or hyperthermia-induced increase in H 2 O 2 might affect synaptic transmission by targeting the most redox-sensitive presynaptic compartment ( Giniatullin et al., 2006 ). However, the effects of H 2 O 2 as a signal molecule have not previously been studied in different patterns of the synaptic activity. Here, using optical and microelectrode recording of synaptic vesicle exocytosis, we studied the use-dependent action of low concentrations of H 2 O 2 and other oxidants in the mouse neuromuscular junction. We found that: (i) H 2 O 2 at low micromole concentrations inhibited both spontaneous and evoked transmitter releases from the motor nerve terminals in a use-dependent manner, (ii) the antioxidant N -acetylcysteine (NAC) eliminated these depressant effects, (iii) the influence of H 2 O 2 was not associated with lipid oxidation suggesting a pure signaling action, (iv) the intracellular oxidant Chloramine-T or (v) the glutathione depletion produced similar to H 2 O 2 depressant effects. Taken together, our data revealed the effective inhibition of neurotransmitter release by ROS, which was proportional to the intensity of synaptic activity at the neuromuscular junction. The combination of various oxidants suggested an intracellular location for redox-sensitive sites responsible for modulation of the synaptic transmission in the skeletal muscle.