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The Journal of Neurophysiology Vol. 85 No. 6 June 2001, pp. 2468-2476
Copyright ©2001 by the American Physiological Society
Departments of Physiology and Neuroscience and Neurosurgery, New York University School of Medicine, New York, New York 10016
Chen, Billy T.,
Marat V. Avshalumov, and
Margaret E. Rice.
H2O2 Is a Novel, Endogenous Modulator of
Synaptic Dopamine Release. J. Neurophysiol. 85: 2468-2476, 2001. Recent evidence
suggests that reactive oxygen species (ROS) might act as modulators of
neuronal processes, including synaptic transmission. Here we report
that synaptic dopamine (DA) release can be modulated by an endogenous
ROS, H2O2. Electrically
stimulated DA release was monitored in guinea pig striatal slices using
carbon-fiber microelectrodes with fast-scan cyclic voltammetry.
Exogenously applied H2O2
reversibly inhibited evoked release in the presence of 1.5 mM
Ca2+. The effectiveness of exogenous
H2O2, however, was
abolished or decreased by conditions that enhance
Ca2+ entry, including increased extracellular
Ca2+ concentration
([Ca2+]o; to 2.4 mM),
brief, high-frequency stimulation, and blockade of inhibitory
D2 autoreceptors. To test whether DA release
could be modulated by endogenous
H2O2, release was evoked in
the presence of the
H2O2-scavenging enzyme,
catalase. In the presence of catalase, evoked
[DA]o was 60% higher than after catalase
washout, demonstrating that endogenously generated
H2O2 can also inhibit DA
release. Importantly, the Ca2+ dependence of the
catalase-mediated effect was opposite to that of
H2O2: catalase had a
greater enhancing effect in 2.4 mM Ca2+ than in
1.5 mM, consistent with enhanced
H2O2 generation in higher [Ca2+]o. Together these
data suggest that H2O2
production is Ca2+ dependent and that the
inhibitory mechanism can be saturated, thus preventing further effects
from exogenous H2O2. These
findings show for the first time that endogenous
H2O2 can modulate vesicular neurotransmitter release, thus revealing an important new signaling role for ROS in synaptic transmission.
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