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J Biol Chem, Vol. 274, Issue 1, 236-240, January 1, 1999

Connexin-43 Hemichannels Opened by Metabolic Inhibition

Scott A. John, Richard Kondo, Sheng-Yong Wang, Joshua I. Goldhaber, and James N. Weiss

From the Cardiovascular Research Laboratory, Departments of Medicine (Cardiology) and Physiology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

The cause of altered ionic homeostasis leading to cell death during ischemia and metabolic inhibition is unclear. Hemichannels, which are precursors to gap junctions, are nonselective ion channels that are permeable to molecules of less than Mr 1000. We show that hemichannels open upon exposure to calcium-free solutions when they are either heterologously overexpressed in HEK293 cells or endogenously expressed in cardiac ventricular myocytes. In the presence of normal extracellular calcium, hemichannels open during metabolic inhibition. During ischemia and other forms of metabolic inhibition, activation of relatively few hemichannels will seriously compromise the cell's ability to maintain ionic homeostasis, which is an essential step promoting cell death.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.



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