Probing deep secrets of muscle fatigue

Jogging along the sand dunes may be liberating for the soul but painful for the muscles. Muscle fatigue is a hot topic attracting a wide range of opinions and comments, many of them ill-informed.

jogger-sand-250wIt has been long known that muscles are readily damaged when they are used as brakes, such as in downhill walking, where leg muscles are forced to repeatedly contract against the pull of gravity.

This lets calcium ions flood into the muscle cells through minute holes in the surface membrane, triggering widespread damage inside the muscle cells.  

Now, researchers at La Trobe University have shown that in normal people this turns on an important cellular repair process.  

Professor Graham Lamb and Dr Robyn Murphy have discovered that the influx of calcium activates a molecule called calpain-3 which steps into action the day after exercise to repair muscle tissues.

The molecule does such a good job that if the same exercise is repeated a week later it will cause no further discomfort.

'Its unclear how the mechanism works,' Professor Lamb says. 'Does calpain 3 actually reprogram the muscle? This is a question for further research.'

The findings of Professor Lambs team could have major implications for various forms of muscular dystrophy.

Their discovery of the role of calpain 3 in muscle repair helps explain cumulative damage in people lacking calpain 3, who develop the 'limb-girdle' form of muscular disease because their muscles progressively degenerate through daily wear and tear.

Probing the depths of muscle fatigue is a contentious field. Misconceptions abound, some of them because assumptions about normal muscle function are made on the basis of laboratory experiments.

Professor Lamb says: 'If you take a muscle out of the body and study it in an organ bath without real blood and oxygen supply and then stimulate it until it fatigues, people think this shows what really goes wrong.

'But if you cut the oxygen and fuel supply to a muscle naturally it malfunctions. People make a lot of unreasonable extrapolations.'

In the La Trobe system, invented by Professor Lamb and Professor George Stephenson, the researchers are able to study the internal environment of the muscle and manipulate the level of ATP- the source of cell energy.

'When the levels of ATP are low, cells stop releasing calcium. Fatigue is the inevitable result. This is a clever cellular mechanism that stops cells from dying.'

The muscle is made up of red and white fibres. White are for power, red for duration. When the white fibres are close to running out of ATP they stop using it and turn themselves off to conserve energy supplies.

A muscle is an exquisite machine, Professor Lamb says. Every part has to work properly. Disease or fatigue can occur through the interruption of any part of the sequence.

He says that the power of muscle mass cannot be overestimated.

'If you build up muscle over a lifetime through regular exercise it can be a good source of protein in the case of disease, substantially increasing your chances of recovery.'

Professor Lambs work is supported by a National Health and Medical Research Council Senior Principal Research Fellowship, the sixth consecutive fellowship he has received over 21 years.  


Contact: Professor Lamb, Email:, Tel: (03) 9479 2249