Myosin Heads and Thick Filaments: Recent and Older Experiments and Hypotheses

The organization and roles of the two heads of myosin in thick filaments from skeletal muscle remain unresolved. Here, I try to reconcile the various points of view. I rec-ommend avoiding comparisons of skeletal muscles from vertebrates (e.g. frog, rabbit, mouse) with those from invertebrates (e.g. tarantula, a spider) and insect flight muscles (IFM; e.g. from Lethocerus). Animal age should also be taken into account, as demon-strated in studies of the contractile properties of isolated skeletal muscles and perme-abilized fibers from young, adult and old mice. The myosin content of natural fila-ments from old and very old rabbits (i.e. animals weighing ~ 5-7 kg) is lower than that of young adult rabbits (i.e. animals weighing ~ 2-3 kg), and their myosin molecules are arranged differently (two strands in older rabbits, three in younger animals). Sarco-penia — the loss of specific contractile force during aging, in particular — can be ex-plained at least partly by the decrease in myosin content (- 1/3) of natural thick fila-ments. Moreover, specific MgATPase activity per myosin molecule (measured in vitro, under resting conditions, in natural thick filaments) is lower in old than in young rab-bits. These two experimental observations probably account for a significant propor-tion of sarcopenia.