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Glutamate release by an Na + load and oxidative stress in nerve terminals: relevance to ischemia/reperfusion
Author(s) -
Tretter Laszlo,
AdamVizi Vera
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01191.x
Subject(s) - veratridine , glutamate receptor , hydrogen peroxide , biophysics , oxidative stress , chemistry , ischemia , biochemistry , sodium , medicine , biology , sodium channel , receptor , organic chemistry
Previously we have reported that oxidative stress induced by hydrogen peroxide exacerbates the effect of an Na + load in isolated nerve terminals, with a consequence of an ATP depletion, [Ca 2+ ] i and [Na + ] i deregulation, and collapse of mitochondrial membrane potential. In the present study, the release of glutamate in response to a combined effect of an [Na + ] load and oxidative stress was measured in isolated nerve terminals over an incubation for 15 min. Exposure to hydrogen peroxide (100 µ m ) had no effect on the release of glutamate, but significantly enhanced the Ca 2+ ‐independent glutamate release induced by a small [Na + ] load achieved with 10 µ m veratridine. The effect of a larger Na + load induced by 40 µ m veratridine was not further increased by hydrogen peroxide; in contrast the external Ca 2+ ‐dependent glutamate release was completely eliminated by the oxidant under this condition. The effects of oxidative stress superimposed on a Na + load are consistent with at least two factors: (i) a relatively modest Na + load induced by veratridine is augmented by H 2 O 2 giving rise to an increased Ca 2+ ‐independent release of glutamate (ii) oxidative stress in combination with a larger Na + load causes severe ATP depletion limiting the Ca 2+ ‐dependent vesicular glutamate release. Given the concurrent presence of an Na + load and oxidative stress in ischemia/reperfusion these results indicate that the extent of the Na + load developing during the ischemic period could determine the release of glutamate induced by an oxidative stress during reperfusion.