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Inhibitory and excitatory neuromodulation by hydrogen peroxide: translating energetics to information
Author(s) -
Lee Christian R.,
Patel Jyoti C.,
O'Neill Brian,
Rice Margaret E.
Publication year - 2015
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.2014.273839
Subject(s) - pars compacta , substantia nigra , neuroscience , chemistry , excitatory postsynaptic potential , biophysics , medium spiny neuron , dopamine , inhibitory postsynaptic potential , striatum , microbiology and biotechnology , biochemistry , biology , dopaminergic
Historically, brain neurochemicals have been broadly classified as energetic or informational. However, increasing evidence implicates metabolic substrates and byproducts as signalling agents, which blurs the boundary between energy and information, and suggests the introduction of a new category for ‘translational’ substances that convey changes in energy state to information. One intriguing example is hydrogen peroxide (H 2 O 2 ), which is a small, readily diffusible molecule. Produced during mitochondrial respiration, this reactive oxygen species, can mediate dynamic regulation of neuronal activity and transmitter release by activating inhibitory ATP‐sensitive K + (K ATP ) channels, as well as a class of excitatory non‐selective cation channels, TRPM2. Studies using ex vivo guinea pig brain slices have revealed that activity‐generated H 2 O 2 can act via K ATP channels to inhibit dopamine release in dorsal striatum and dopamine neuron activity in the substantia nigra pars compacta. In sharp contrast, endogenously generated H 2 O 2 enhances the excitability of GABAergic projection neurons in the dorsal striatum and substantia nigra pars reticulata by activating TRPM2 channels. These studies suggest that the balance of excitation vs . inhibition produced in a given cell by metabolically generated H 2 O 2 will be dictated by the relative abundance of H 2 O 2 ‐sensitive ion channel targets that receive this translational signal.