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Science 3 October 1997:
Vol. 278. no. 5335, pp. 114 - 117
DOI: 10.1126/science.278.5335.114
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Reports

Mediation of Neuronal Apoptosis by Enhancement of Outward Potassium Current

Shan Ping Yu, Chen-Hsiung Yeh, Stefano L. Sensi, Byoung J. Gwag, Lorella M. T. Canzoniero, Z. Shadi Farhangrazi, Howard S. Ying, Min Tian, Laura L. Dugan, Dennis W. Choi *

Apoptosis of mouse neocortical neurons induced by serum deprivation or by staurosporine was associated with an early enhancement of delayed rectifier (IK) current and loss of total intracellular K+. This IK augmentation was not seen in neurons undergoing excitotoxic necrosis or in older neurons resistant to staurosporine-induced apoptosis. Attenuating outward K+ current with tetraethylammonium or elevated extracellular K+, but not blockers of Ca2+, Cl-, or other K+ channels, reduced apoptosis, even if associated increases in intracellular Ca2+ concentration were prevented. Furthermore, exposure to the K+ ionophore valinomycin or the K+-channel opener cromakalim induced apoptosis. Enhanced K+ efflux may mediate certain forms of neuronal apoptosis.

Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed at the Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. E-mail: choid{at}neuro.wustl.edu

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Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production.
S. L. Sensi, H. Z. Yin, S. G. Carriedo, S. S. Rao, and J. H. Weiss (1999)
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An Ultraviolet-activated K+ Channel Mediates Apoptosis Of Myeloblastic Leukemia Cells.
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Transient Neurophysiological Changes in CA3 Neurons and Dentate Granule Cells After Severe Forebrain Ischemia In Vivo.
T. M. Gao, E. M. Howard, and Z. C. Xu (1998)
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Ceramide Inhibits Inwardly Rectifying K+ Currents via a Ras- and Raf-1-Dependent Pathway in Cultured Oligodendrocytes.
H. Hida, M. Takeda, and B. Soliven (1998)
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Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function.
E. L. Holmuhamedov, S. Jovanovic, P. P. Dzeja, A. Jovanovic, and A. Terzic (1998)
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Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K+ channels.
V. Avdonin, J. Kasuya, M. A. Ciorba, B. Kaplan, T. Hoshi, and L. Iverson (1998)
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Potassium Leakage During the Apoptotic Degradation Phase.
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The c-Src Tyrosine Kinase Regulates Signaling of the Human DF3/MUC1 Carcinoma-associated Antigen with GSK3beta and beta -Catenin.
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Activation of Potassium and Chloride Channels by Tumor Necrosis Factor alpha . ROLE IN LIVER CELL DEATH.
H. H. Nietsch, M. W. Roe, J. F. Fiekers, A. L. Moore, and S. D. Lidofsky (2000)
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Plasma Membrane Depolarization without Repolarization Is an Early Molecular Event in Anti-Fas-induced Apoptosis.
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