The diaphragm as a striated muscle is characterized by the repetition of a single
element arranged in series: the sarcomere containing two kinds of myofilaments: a thick one constituted by the
myosin, and a thin one primarily composed of actin. The
myosin molecule consists of two heads where two
myosin heavy chains (MHC) are fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails. The diaphragm contains 4 MHC
isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6 MLC
isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-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 from the MHC-slow to the MHC-2A, MHC-2B and MHC-2X/2B. According to the circumstances, the diaphragm will adapt towards a slow profile (
COPD,
cardiac failure and in animals:
Duchenne muscular dystrophy,
denervation-1 week, age-female,
corticosteroids, chronic stimulation), or a fast profile (in animals: chronic
hypoxia,
denervation-2 weeks, age-males) or a more oxidative profile (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 pathological situation, several factors are able to influence the fiber composition of the diaphragm. Therefore, the net result of the influence of these different factors in terms of MHC and MLC diaphragm adaptation is difficult to predict.