In a report published Monday in an early online edition of Proceedings of the National Academy of Sciences, Dr. Marks says the problem is calcium flow inside muscle cells. Ordinarily, ebbs and flows of calcium in cells control muscle contractions. But when muscles grow tired, the investigators report, tiny channels in them start leaking calcium, and that weakens contractions. At the same time, the leaked calcium stimulates an enzyme that eats into muscle fibers, contributing to the muscle exhaustion. [Snip]There is discussion in the article of a drug being developed to correct the problem of calcium leaks, but any effective medications are a long way off. What really matters is that researchers are beginning to have a greater understanding of muscle fatigue, and that understanding is going to result is new ways of getting the human body to work better.
Dr. Marks, a cardiologist, wanted to discover better ways to treat people with congestive heart failure, a chronic and debilitating condition that affects an estimated 4.8 million Americans.
Its hallmark is a damaged heart, usually from a heart attack or high blood pressure. Struggling to pump blood, the heart grows, sometimes becoming so large that it fills a patient’s chest. As the disease progresses, the lungs fill with fluid. Eventually, with congested lungs and a heart that can barely pump, patients become so short of breath that they cannot walk across a room. Half die within five years.
In his efforts to understand why the heart muscle weakened, Dr. Marks focused on the molecular events in the heart. He knew the sequence of events. As the damaged heart tries to deal with the body’s demands for blood, the nervous system floods the heart with the fight or flight hormones, epinephrine and norepinephrine that make the heart muscle cells contract harder.
The intensified contractions, Dr. Marks and his colleagues discovered, occurred because the hormones caused calcium to be released into the heart muscle cells’ channels.
But eventually the epinephrine and norepinephrine cannot stimulate the heart enough to meet the demands for blood. The brain responds by releasing more and more of those fight or flight hormones until it is releasing them all the time. At that point, the calcium channels in heart muscle are overstimulated and start to leak.
When they understood the mechanisms, the researchers developed a class of experimental drugs that block the leaks in calcium channels in the heart muscle. The drugs were originally created to block cells’ calcium channels, a way of lowering blood pressure.
Dr. Marks and his colleagues altered the drugs to make them less toxic and to rid them of their ability to block calcium channels. They were left with drugs that stopped calcium leaks. The investigators called the drugs rycals, because they attach to the ryanodine receptor/calcium release channel in heart muscle cells. The investigators tested rycals in mice and found that they could prevent heart failure and arrhythmias in the animals. [Snip]
Dr. Marks wondered whether the mechanism he discovered might apply to skeletal muscle as well as heart muscle. Skeletal muscle is similar to heart muscle, he noted, and has the same calcium channel system. And heart failure patients complain that their muscles are extremely weak.
“If you go to the hospital and ask heart failure patients what is bothering them, they don’t say their heart is weak,” Dr. Marks said. “They say they are weak.”
So he and his colleagues looked at making mice exercise to exhaustion, swimming and then running on a treadmill. The calcium channels in their skeletal muscles became leaky, the investigators found. And when they gave the mice their experimental drug, the animals could run 10 to 20 percent longer.
Then, collaborating with David Nieman, an exercise scientist at Appalachian State University in Boone, N.C., the investigators asked whether the human skeletal muscles grew tired for the same reason, calcium leaks.
Highly trained bicyclists rode stationary bikes at intense levels of exertion for three hours a day three days in a row. For comparison, other cyclists sat in the room but did not exercise.
Dr. Nieman removed snips of thigh muscle from all the athletes after the third day and sent them to Columbia, where Dr. Marks’s group analyzed them without knowing which samples were from the exercisers and which were not. The results, Dr. Marks said, were clear. The calcium channels in the exercisers leaked. A few days later, the channels had repaired themselves. The athletes were back to normal.
We all experience muscle fatigue, and the researchers are only just now getting a better handle on understanding of it. Could these findings shed light on Chronic fatigue syndrome and Fibromyalgia?
This article leads me to a speculation. I use caffeine (coffee or tea) when I am feeling fatigue. Caffeine causes a physical reaction similar to the fight or flight mechanism. Noting the description above of how the body puts out the fight or flight hormones of epinephrine and norepinephrine to make the muscle cells contract harder when they are fatigued, I wonder how the caffeine and calcium leakages interact?
I also wonder how many other physical, emotional and mental events we all experience are just waiting to be unraveled this way.
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