That explanation has been pretty much laid to rest recently, and the NY Times article from February 12 (I'm just getting around to catching up on the news feeders) finds another likely explanation in leaky calcium ion channels :
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.
There's a graphic that I'll post below, but it will probably disappear soon. It isn't really all that helpful:
It also leaves open the question as to why the calcium channels become leaky in the first place. Is it a change in pH, temperature, physical stress on the proteins that make up the channel? That question isn't even raised in the Times article. The obvious issue that is raised is the potential for abuse in competitive athletics of therapies to combat fatigue (the study was initially designed to find ways to combat cardiac muscle fatigue from heart disease). The investigators in this study were able to reduce fatigue in skeletal muscle of mice using drugs called rycals, which stopped the leaky calcium channels, and allowed the mice to continue exercise for 10 - 20% longer than without the drug. There's an interesting speculation at the end of the article about the utility of muscle fatigue:
“Maybe this is a protective mechanism,” he said. “Maybe fatigue is saying that you are getting ready to go into a danger zone. So it is cutting you off. If you could will yourself to run as fast and as long as you could, some people would run until they keeled over and died.”
Just ask Pheidippides.
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