In this study, they looked at the effects of oxidative stress on unpaired (or non-junctional) hemichannels found in the membrane of cells from the lungs and the heart--the primary targets of cigarette smoke.
When they exposed these cells to low levels of an extract made from cigarette smoke, the non-junctional hemichannels opened. This allowed toxic molecules found in the smoke to flow directly into the cell, and vital metabolites such as ATP and NAD, to leak out, leading, ultimately, to cell injury and death.
Drugs that prevented hemichannels from opening protected the cells from similar exposures. Treating the cells with silencing RNA for the hemichannel protein also protected cells by preventing the creation of these channels.
"It required very little stress to open these channels," Lal said. "Substances found in smoke and other pollutants can alter the electrical potential of the cells membrane. A small shift in the membranes electrical potential, which we know occurs in many oxidative stress situations, appears to open these channels and allow unregulated flow. This can weaken and kill cells."
Cells have multiple membrane channels that carefully control the flow of specific small molecules in and out of the cell, including calcium, sodium and potassium ions, each of which passes through a specific type of channel.
Hemichannels, however, with ports nearly twice the size of an ion channel, are not as specific, permitting more rapid, less regulated flow of molecules up to the size of 1000 Daltons--wide enough to allow exchange of many signaling and messenger molecules, such as ATP and small metabolites that are essential for normal cell susten
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Contact: John Easton
John.Easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
6-Aug-2007