February 12, 2008
Finding May Solve Riddle of Fatigue in Muscles
By GINA KOLATA
One of the great unanswered questions in physiology is why muscles get tired. The
experience is universal, common to creatures that have muscles, but the answer has been
elusive until now.
Scientists at Columbia say they have not only come up with an answer, but have also
devised, for mice, an experimental drug that can revive the animals and let them keep
running long after they would normally flop down in exhaustion.
For decades, muscle fatigue had been largely ignored or misunderstood. Leading
physiology textbooks did not even try to offer a mechanism, said Dr. Andrew Marks,
principal investigator of the new study. A popular theory, that muscles become tired
because they release lactic acid, was discredited not long ago.
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.
In recent years, says George Brooks of the University of California, Berkeley, muscle
researchers have had more or less continuous discussions about why muscles fatigue. It
was his work that largely discredited the lactic-acid hypothesis, but that left a void.
What did make muscles tired?
The new work in mice, Dr. Brooks said, “is exciting and provocative.” It is a finding that
came unexpectedly from a very different line of research. 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.