Clinical pertinence of myosin isoform distribution in the diaphragmatic muscle

The diaphragm as a striated muscle is characterized by the repetition of a single element arranged in series: the sarcomere containing two kinds of my ofilaments: a thick one constituted by the myosin, and a thin one primarily composed of actin. The myosin molecule consists of two heads where two myo sin heavy chains (MHC) are fired a flexible hinge with two light (MLC) chai ns, and long rad-shaped tails. The diaphragm contains 4 MHC isoforms (MHC-s low, MHC-2A, MHC-2B, MHC-2X) and 6 MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, M LC-1sb, MLC-2f, MLC-2s/v). In humans, the diaphragm contains mainly fibers expressing the isoforms MHC-slow: MHC-2A, and MLC-2f MLC-2s et MLC-1f: For the mechanical properties of the different isoforms, there is a gradient fr om the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circu mstances, the diaphragm will adapt towards a slow profile (COPD, cardiac fa ilure and in animals: Duchenne muscular dystrophy, denervation-1 week, age- female, corticosteroids, chronic stimulation), or a fast profile (in animal s: chronic hypoxia, denervation-2 weeks, age-males) or a more oxidative pro file (in animals: cachexia, obesity). The reasons why the diaphragm adapts towards a slower or a faster muscle are not known. In fact, for a given pat hological situation, several factors are able to influence the fiber compos ition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficul t to predict.