Modulation of the GABA[sub A] -gated chloride channel by reactive oxygen species.

Autor: Sah, Renu, Galeffi, Francesca, Ahrens, Rebecca, Jordan, Gwendolyn, Schwartz-Bloom, Rochelle D
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Zdroj: Journal of Neurochemistry; 2/1/2002, Vol. 80 Issue 3, p383, 9p, 5 Black and White Photographs, 2 Charts, 4 Graphs
Abstrakt: The accumulation of reactive oxygen species during cellular injury leads to oxidative stress. This can have profound effects on ionic homeostasis and neuronal transmission. γ-Aminobutyric acid (GABA) neurotransmission is sensitive to reactive oxygen species, but most studies have indicated that this is due to alterations in GABA release. Here, we determined whether reactive oxygen species can alter GABA[sub A] receptor-gated Cl[sup –] channels in the adult hippocampus. First, we measured the effects of hydrogen peroxide on intracellular Cl[sup –] using UV laser scanning confocal microscopy and the Cl[sup –] -sensitive probe, 6-methoxy-N -ethylquinolium iodide (MEQ). Superfusion of adult rat hippocampal slices with hydrogen peroxide for 10 min decreased MEQ fluorescence (elevation in [Cl[sup –] ][sub i] ) significantly in area CA1 pyramidal cell soma. Alterations in [Cl[sup –] ][sub i] were prevented by the vitamin E analog Trolox, an antioxidant that scavenges free radicals. After exposure of slices to hydrogen peroxide, the ability of the GABA agonist muscimol to increase [Cl[sup –] ][sub i] was attenuated. To determine if GABA[sub A] receptors were sensitive to oxidative insults, the effect of hydrogen peroxide on the binding of [[sup 35] S]t -butylbicyclophosphorothionate (TBPS) to GABA-gated Cl[sup –] channels was measured using receptor autoradiography and homogenate binding assays. Hydrogen peroxide inhibited [[sup 35] S]TBPS binding in a regionally selective manner, with the greatest inhibition in cerebral cortex, hippocampus and striatum, areas␣vulnerable to oxidative stress. Similarly, xanthine and xanthine oxidase, which generate superoxide radicals, reduced [[sup 35] S]TBPS binding in these regions. The effect of hydrogen peroxide on [[sup 35] S]TBPS binding was non-competitive and was prevented by Trolox and the iron chelator, deferoxamine. We conclude that reactive oxygen species may... [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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