Response of a fast muscle from normal and dystrophic (dy2j) mice to a local decrease in extracellular Ca2+ induced at different stages of postnatal life.

It has previously been reported that reducing Ca2+ entry into muscle fibres was beneficial to dystrophic muscles. In this study, we examined the effect, on the force output and contractile properties of the tibialis anterior muscle, of a local decrease in extracellular Ca2+, produced in normal and dystrophic mice at various stages of postnatal life by applying a small strip of silicon rubber containing a calcium chelator (BAPTA). Lowering extracellular Ca2+ in this way at an early stage of postnatal life (11-16 days) interferes with normal development in that, 3-5 weeks after the initial operation, the treated TA muscles from normal mice are weaker and their contractile speed is slower than that of their untreated counterparts. In contrast, the same procedure has a beneficial effect on dystrophic muscles in that they produce more force than untreated controls. Our results show that these changes are not related to changes in the total number of muscle fibres or fibre type proportions. These changes are temporary and by 8-12 weeks after the operation, the treated muscles are indistinguishable from controls. Finally, our results also indicate that skeletal muscles from older animals, both normal and dystrophic, become insensitive to this manipulation. These results provide the first evidence for a difference in the sensitivity of normal immature and normal adult skeletal muscles to their extracellular Ca2+ environment. They also suggest that in this context, dystrophic muscles might already differ from normal at a stage prior to the clinical expression of the symptoms of the disease.