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Next Article 
The Journal of Neuroscience, May 1, 1998, 18(9):3117-3123
Disruption of Mitochondrial Respiration Inhibits Volume-Regulated
Anion Channels and Provokes Neuronal Cell Swelling
Amanda J.
Patel,
Inger
Lauritzen,
Michel
Lazdunski, and
Eric
Honoré
Institut de Pharmacologie Moléculaire et Cellulaire, Centre
National de la Recherche Scientifique, UPR 411, 06560 Valbonne, France.
Hypoxia and inhibitors of mitochondrial respiration impair the
regulatory volume decrease (RVD) of cerebellar granule neurons after
hypotonic swelling. RVD is linked to the opening of volume-regulated anion channels (VRACs). VRACs are outwardly rectifying, inactivate slowly during maintained depolarization, and are permeable to the
cellular organic osmolyte taurine. Channel activation requires nonhydrolytic ATP binding and is not modulated by intracellular ADP.
VRAC opening is reversibly depressed by hypoxia and by mitochondrial inhibitors such as oligomycin, rotenone, and antimycin A. These results
demonstrate that neuronal VRAC activation and swelling are both tightly
linked to cellular energy. Moreover, the findings reported in this work
may have a particular significance for inherited mitochondrial human
diseases, such as mitochondrial myopathy, encephalopathy, lactic
acidosis, and stroke-like episodes (MELAS), which cause brain swelling
and edema.
Key words:
cerebellar granule neurons; RVD; chloride channels; ICln; hypoxia; mitochondrial encephalopathy
Copyright © 1998 Society for Neuroscience 0270-6474/98/1893117-07$05.00/0
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