It is widely thought that in Duchenne's muscular dystrophy, the muscular cells death is linked with disruption of Ca2+ homeostasis and oxidative stress. The permeability transition pore is an inner membrane channel inhibed by Cyclosporin A which might participate to mitochondrial Ca2+ homeostasis and which is a target of oxidative stress. The irreversible opening of permeability transition pores leads to a collapse of ATP synthesis and induces cell death.
Mdx mice is an established animal model of Duchenne's muscular dystrophy. We intend to (1) investigate intracellular Ca2+ homeostasis in two types of muscle fibers: skeletal muscle which will undergo cell death, and extraocular muscle which is spared by the disease; (2) find out whether mitochondrial function is differentially regulated in these two types of muscle fibers; (3) study the effects of Cyclosporin A on the response of the permeability transition pore to conditions of oxidative stress and Ca2+ overload.