Premium
Dual Action of Hydrogen Peroxide on Synaptic Transmission at the Frog Neuromuscular Junction
Author(s) -
Giniatullin A. R.,
Giniatullin R. A.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.050690
Subject(s) - neuromuscular junction , neurotransmission , chemistry , neuromuscular transmission , protein kinase c , biophysics , long term potentiation , stimulation , pharmacology , endocrinology , biochemistry , neuroscience , biology , kinase , receptor
There is evidence that reactive oxygen species (ROS) are produced and released during neuromuscular activity, but their role in synaptic transmission is not known. Using a two‐electrode voltage‐clamp technique, at frog neuromuscular junctions, the action H 2 O 2 on end‐plate currents (EPC) was studied to determine the targets for this membrane‐permeable ROS. In curarized or cut muscles, micromolar concentrations of H 2 O 2 increased the amplitude of EPCs. Higher (> 30 μ m ) doses inhibited EPCs and prolonged current decay. These effects were presynaptic since H 2 O 2 did not change the amplitude or duration of miniature EPCs (although it reduced the rate of spontaneous release at high concentrations). Quantal analysis and deconvolution methods showed that facilitation of EPCs was due to increased quantal release, while depression was accompanied by temporal dispersion of evoked release. Extracellular recordings revealed prolonged presynaptic Ca 2+ entry in the presence of high H 2 O 2 . Both low and high H 2 O 2 increased presynaptic potentiation during high‐frequency stimulation. Pro‐oxidant Fe 2+ did not affect facilitation by low doses of H 2 O 2 but augmented the inhibition of EPCs by high H 2 O 2, indicating involvement of hydroxyl radicals. High Mg 2+ and the ROS scavenger N ‐acetylcysteine eliminated both the facilitatory and depressant effects of H 2 O 2 . The facilitatory effect of H 2 O 2 was prevented by protein kinase C (PKC) inhibitors and 4β‐phorbol 12‐myristate, 13‐acetate (PMA), an activator of PKC. PKC inhibitors but not PMA also abolished the depressant effect of H 2 O 2 . Our data suggest complex presynaptic actions of H 2 O 2 , which could serve as a fast feedback modulator of intense neuromuscular transmission.