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Exacerbated responses to oxidative stress by an Na+ load in isolated nerve terminals: the role of ATP depletion and rise of [Ca2+](i)

Chinopoulos, Christos and Tretter, László and Rózsa, Adrienn and Ádám, Veronika (2000) Exacerbated responses to oxidative stress by an Na+ load in isolated nerve terminals: the role of ATP depletion and rise of [Ca2+](i). JOURNAL OF NEUROSCIENCE, 20 (6). pp. 2094-2103. ISSN 0270-6474

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Abstract

We have explored the consequences of a [Na 1 ] i load and oxidative stress in isolated nerve terminals. The Na 1 load was achieved by veratridine (5–40 m M ), which allows Na 1 entry via a voltage-operated Na 1 channel, and oxidative stress was induced by hydrogen peroxide (0.1–0.5 m M ). Remarkably, nei- ther the [Na 1 ] i load nor exposure to H 2 O 2 had any major effect on [Ca 2 1 ] i , mitochondrial membrane potential ( D c m), or ATP level. However, the combination of an Na 1 load and oxidative stress caused ATP depletion, a collapse of D c m, and a pro- gressive deregulation of [Ca 2 1 ] i and [Na 1 ] i homeostasis. The decrease in the ATP level was unrelated to an increase in [Ca 2 1 ] i and paralleled the rise in [Na 1 ] i . The loss of D c m was prevented in the absence of Ca 2 1 but unaltered in the presence of cyclosporin A. We conclude that the increased ATP con- sumption by the Na,K–ATPase that results from a modest [Na 1 ] i load places an additional demand on mitochondria met- abolically compromised by an oxidative stress, which are un- able to produce a sufficient amount of ATP to fuel the ATP- driven ion pumps. This results in a deregulation of [Na 1 ] i and [Ca 2 1 ] i , and as a result of the latter, collapse of D c m. The vicious cycle generated in the combined presence of Na 1 load and oxidative stress could be an important factor in the neuro- nal injury produced by ischemia or excitotoxicity, in which the oxidative insult is superimposed on a disturbed Na 1 homeostasis.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 19 Jul 2017 10:59
Last Modified: 19 Jul 2017 10:59
URI: http://real.mtak.hu/id/eprint/56654

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