Cause Of Muscle Fatigue Identified

New evidence indicates that calcium contributes to muscle fatigue (Proc. Natl. Acad. Sci. USA 2008, 105, 2198). The finding could lead to drugs that improve endurance in soldiers, athletes, or in patients who suffer debilitating fatigue as a result of chronic heart failure. Muscles consist of numerous muscle fibers that each contain a bundle of myofibrils sheathed in a membranous network known as the sarcoplasmic reticulum. For a muscle to contract, calcium must diffuse out of the network through calcium channels and bind to the myofibrils. The muscle relaxes when calcium detaches from the myofibrils and is pumped back into the network. Columbia University's Andrew R. Marks and coworkers found that intense exercise modifies the protein complex that normally keeps the calcium channel closed, allowing extra calcium to flood the myofibrils. The leak weakens the force produced by the muscle and activates an enzyme that damages the muscle fibers. The researchers discovered that an experimental drug (shown) can prevent the leakage and increase endurance in mice.