The effect of denervation and dystrophy on the adaptation of sarcomere number to the functional length of the muscle in young and adult mice.

In young animals the elongation of the limb bones increases the functional lengths of the muscles. In adult animals the functional length of a muscle can be increased by immobilizing it in the lengthened position. In both cases the muscle adapts by adding on more sarcomeres in series. The role of the nerve supply in this adaptation has been investigated using denervated muscles and muscles from dystrophic animals where there is thought to be an abnormality of the nerve supply. Postnatal sarcomere addition in denervated muscles falls short of that of controls. Although this might mean that the nerve supply is necessary for normal addition of sarcomeres, it is just as likely that there is a change in gait resulting from denervation, which affects the sarcomere number. Sarcomere number in fully grown mice is not affected by denervation, nor is the ability of the muscle to adapt to immobilization in the lengthened position. This is true for fast-twitch as well as slow-twitch muscles. In dystrophic muscles postnatal sarcomere addition is normal, although the presence of a few short fibres in the muscle may mean that some muscle fibres cannot adapt to an increase in the functional length of the muscle accompanying bone growth. Adult dystrophic muscle is capable of adapting to immobilization in the lengthened position. However, although the total number of additional sarcomeres is the same as in normal immobilized muscle, they are added on at a slower rate. The experiments show that although denervated and dystrophic muscle fibres are in a state of atrophy they are still capable of adding on sarcomeres in series when the functional length of the muscle is increased. It would appear that the mechanism which enables the muscle to respond in this way to an increased functional length does not involve the nerve supply. This work was supported by a grant from the National Fund for Research into Crippling Diseases.