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Science 298 (5595): 1029-1033

Copyright © 2002 by the American Association for the Advancement of Science

Cytoprotective Role of Ca2+- Activated K+ Channels in the Cardiac Inner Mitochondrial Membrane

Wenhong Xu,1 Yongge Liu,2 Sheng Wang,2 Todd McDonald,3 Jennifer E. Van Eyk,3 Agnieszka Sidor,1 Brian O'Rourke1*

Ion channels on the mitochondrial inner membrane influence cell function in specific ways that can be detrimental or beneficial to cell survival. At least one type of potassium (K+) channel, the mitochondrial adenosine triphosphate-sensitive K+ channel (mitoKATP), is an important effector of protection against necrotic and apoptotic cell injury after ischemia. Here another channel with properties similar to the surface membrane calcium-activated K+ channel was found on the mitochondrial inner membrane (mitoKCa) of guinea pig ventricular cells. MitoKCa significantly contributed to mitochondrial K+ uptake of the myocyte, and an opener of mitoKCa protected hearts against infarction.

1 Institute of Molecular Cardiobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Maryland Research Laboratories, Otsuka Maryland Research Institute, Rockville, MD 20850, USA.
3 Department of Physiology, Queen's University, Kingston, Ontario, K7L 3N6 Canada.
*   To whom correspondence should be addressed. E-mail: bor{at}jhmi.edu.

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Opening of Ca2+-activated K+ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice.
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   Abstract »    Full Text »    PDF »
Multiprotein complex containing succinate dehydrogenase confers mitochondrial ATP-sensitive K+ channel activity.
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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D. Trauner and R. H. Kramer (2004)
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   Abstract »    Full Text »    PDF »
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C. M. O'Reilly, K. E. Fogarty, R. M. Drummond, R. A. Tuft Jr., and J. V. Walsh (2004)
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   Abstract »    Full Text »    PDF »
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J. Gen. Physiol. 123, 471-473
   Full Text »    PDF »
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B. O'Rourke (2004)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Role of the Mitochondrial Permeability Transition in Myocardial Disease.
J. N. Weiss, P. Korge, H. M. Honda, and P. Ping (2003)
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   Abstract »    Full Text »    PDF »
Mitochondrial plasticity in classical ischemic preconditioning--moving beyond the mitochondrial KATP channel.
J. Minners, C. J. McLeod, and M. N. Sack (2003)
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   Abstract »    Full Text »    PDF »
Matrix volume measurements challenge the existence of diazoxide/glibencamide-sensitive KATP channels in rat mitochondria.
M. Das, J. E Parker, and A. P Halestrap (2003)
J. Physiol. 547, 893-902
   Abstract »    Full Text »    PDF »
Differential Actions of Cardioprotective Agents on the Mitochondrial Death Pathway.
M. Akao, B. O'Rourke, H. Kusuoka, Y. Teshima, S. P. Jones, and E. Marban (2003)
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   Abstract »    Full Text »    PDF »
Minerva.
(2002)
BMJ 325, 1122
   Full Text »    PDF »

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