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Molecular 'Valve' Tied to Recovery from Heart Attack

Drugs that keep it open prevent damage in animals

THURSDAY, Oct. 31, 2002 (HealthDayNews) -- Drugs that open a kind of cellular carburetor may help prevent rampant damage in the wake of heart attacks, new research has found.

Heart attacks occur when blood flow to the organ's muscle cells is blocked. Specifically, the loss of oxygen prevents cell engines called mitochondria from generating ATP, the chemical fuel that drives life. Deprived of energy, heart muscle dies. Depending on the spread of this damage, the pump can weaken or fail completely.

However, researchers in the United States and Canada have found a molecular valve inside mitochondria that appears to help match energy supply with energy demand in the heart (and other organs, too). The valve, called an ion channel, regulates the flow of potassium ions, and when these positively charged atoms are allowed to pass freely through the channel into the mitochondria, heart muscle is less vulnerable to an attack.

"The heart is pumping 24 hours a day, year after year. By age 75 it has pumped more than 2 billion times without stopping, and it needs a continuous supply of energy," says Brian O'Rourke, a cell physiologist at Johns Hopkins University School of Medicine in Baltimore and a co-author of the new study.

"When you have a heart attack the fuel gets shut off, and some cells die a slow or a quick death. Somehow this channel improves that. They don't die," O'Rourke says. He and his colleagues report the findings in tomorrow's issue of Science.

In one experiment, the team used charybdotoxin -- a poison derived from scorpions -- to freeze the activity of the channel, dubbed mitoKCa because it responds to signals from calcium. Regular floods of calcium into heart muscle cells makes them contract.

Then, their collaborators at the Otsuka Maryland Research Institute showed they could cut the damage from heart attacks in rabbits in half by pre-treating them with a drug that keeps the potassium channel open.

O'Rourke says potassium channel opening drugs could one day help prevent cell death from heart attacks or heart procedures such as bypass surgery or angioplasty. They may also be useful in fighting damage associated with stroke, Alzheimer's disease and other brain disorders.

However, he adds, it's far too soon to know if such an approach works in people. "It's sort of an untapped area right now," he says.

Elizabeth Murphy, a cell signaling expert at the National Institute of Environmental Health Sciences who was familiar with O'Rourke's research, says it could one day have "great therapeutic potential" for heart patients. However, drug makers must first develop potassium ion channel activators that are specific to heart muscles, Murphy adds, since interfering with cells in other organ systems, such as blood vessels, might have unwanted effects.

What To Do

For more on how the heart functions, try the Cleveland Clinic. To learn about the warning signs of a heart attack, visit the American Heart Association.

SOURCES: Brian O'Rourke, Ph.D., associate professor, medicine, Johns Hopkins University School of Medicine, Baltimore; Elizabeth Murphy, Ph.D., senior scientist, National Institute of Environmental Health Sciences, Research Triangle Park, N.C.; Nov. 1, 2002, Science
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