Spotlight on Research for 2002

May 2002 (historical)

Enzyme is Key in Sustained Muscle Activity, Say Scientists

Researchers supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases have discovered that an enzyme called calcium/calmodulin-dependent protein kinase (CaMK) is a major player in activating "slow-twitch" muscles-those involved in sustained exercise like swimming or running.

A University of Texas Southwestern Medical Center team directed by R. Sanders Williams, M.D.*, developed a mouse model that produced high amounts of this enzyme in its skeletal muscle. The animals' muscles showed increased numbers of mitochondria, the energy-producing micromachines in cells, mimicking the mitochondrial increase associated with endurance exercise. The mice were also more resistant to fatigue after repeated muscle contractions, and their muscles showed increased activity of mitochondrial enzymes important in fatty acid metabolism and electron transport. In addition, CaMK was found to activate the gene PGC-1, the "master regulator" of mitochondrial proliferation in mouse muscle cells.

Some have speculated that the discovery of these effects could eventually form the science base for developing an "exercise pill." Such a pill, they say, would influence muscle-signaling pathways to confer muscle activity benefits on people whose health conditions prohibit exercising, including those with heart and respiratory conditions.


Wu H, Kanatous S, Thurmond F, Gallardo T, Isotani E, Bassel-Duby R, Williams R. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 2002; 296:349-352.

*Dr. Williams is now Dean of the School of Medicine and Vice Chancellor for Academic Affairs at Duke University