A series of experiments in laboratory dishes and in animals implicates a recently described class of membrane ion channels, called acid-sensing ion channels (ASICs), to the influx of calcium in nerve cells starved of oxygen and subjected to acidic conditions. That calcium overload, long attributed to another group of cellular components, is essential for stroke injury as it sets off a cascade of events toxic to cells, said neurophysiologist and lead author of the study (Zhi-Gang Xiong of Robert S. Dow Neurobiology Laboratories in Portland, Oregon).
What's more, the team reports, rats injected with agents known to block ASICs--including the venom of a tarantula spider--exhibited a reduction in brain damage from ischemia. Mice lacking a functional copy of the ASIC gene were similarly resistant to stroke damage, they found.
"Our study offers multiple lines of evidence that reveal acid-sensing ion channels as major players in the damage suffered by stroke victims," Xiong said. "Furthermore, we found that existing pharmacologic agents that block those channels can dramatically reduce the amount of brain injury."
In the United States, stroke is the leading cause of severe, long-term disability and the third leading cause of death, according to the American Stroke Association. About 700,000 Americans have a stroke each year--one every 45 seconds.
A type of cardiovascular disease, stroke affects arteries of the brain. In ischemic stroke, the most common form, a blood vessel that carries oxygen a
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Cell Press
16-Sep-2004