Sarcomere level mechanics of the fast skeletal muscle of the medaka fish larva

: The medaka fish (Oryzias latipes) is a vertebrate model used in developmental biology and genetics. Here we explore its suitability as a model for investigating the molecular mechanisms of human myopathies caused by mutations in sarcomeric proteins. To this end, the relevant mechanical parameters of the intact skeletal muscle of wild type medaka are determined using the transparent tail at larval stage 40. Tails were mounted at sarcomere length 2.1 μm in a thermoregulated trough containing physiological solution. Tetanic contractions were elicited at physiological temperature (10-30°C) by electrical stimulation and sarcomere length changes were recorded with nanometre-microsecond resolution during both isometric and isotonic contractions with a striation follower. The force output has been normalised for the actual fraction of the cross-section of the tail occupied by the myofilament lattice, as established with TEM, and then for the actual density of myofilaments, as established with X-ray diffraction. Under these conditions, the mechanical performance of the contracting muscle of the wild-type larva can be defined at the level of the half-thick filament, where ~300 myosin motors work in parallel as a collective motor, allowing a detailed comparison with the established performance of the skeletal muscle of different vertebrates. The results of this study point out that the medaka fish larva is a suitable model for the investigation of the genotype/phenotype correlations and therapeutic possibilities in skeletal muscle diseases caused by mutations in sarcomeric proteins.