RT Journal Article
SR Electronic
T1 Disruption of Mitochondrial Respiration Inhibits Volume-Regulated Anion Channels and Provokes Neuronal Cell Swelling
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3117
OP 3123
DO 10.1523/JNEUROSCI.18-09-03117.1998
VO 18
IS 9
A1 Amanda J. Patel
A1 Inger Lauritzen
A1 Michel Lazdunski
A1 Eric Honoré
YR 1998
UL http://www.jneurosci.org/content/18/9/3117.abstract
AB 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.