Connexin-43 Hemichannels Opened by Metabolic Inhibition*
Abstract
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 thanM r 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.
Footnotes
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↵* This work was supported by National Institutes of Health Specialized Center of Research in Sudden Cardiac Death P01 HL52319, National Institutes of Health Grants RO1 HL36729, RO1 HL44880, and R29 HL51129, by a grant-in-aid (to S. A. J.) and research fellowship (to R. K.) from the American Heart Association, Greater Los Angeles Affiliate, and by the Laubisch Fund, the Chizuko Kawata Endowment, and the Maude Cody Guthman Endowment.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Cardiovascular Research Laboratory, Depts. of Medicine (Cardiology) and Physiology, University of California at Los Angeles School of Medicine, 675 Circle Dr. South, Los Angeles, CA 90095. Tel.: 310-825-9029; Fax: 310-206-5777; E-mail: jweiss{at}mednet.ucla.edu.
- GFP
- green fluorescent protein
- Cx
- connexin
- FCCP
- carbonyl cyanide-p-trifluoromethoxyphenylhydrazone
- IAA
- iodoacetate
- MI
- metabolic inhibition.
- Received August 28, 1998.
- Revision received October 13, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
