Aim: 

Skeletal muscle functional plasticity is to a large extent determined by the existence of isoforms of the myosin heavy chain (MHC) portion of the myosin molecule. In skeletal muscle of adult small mammals, 4 isoforms are normally expressed (MHC-1, MHC-2A, MHC-2X and MHC-2B) giving rise to 4 pure fibre types whose velocity of shortening, power and ATPase increases in the order type 1 < 2A < 2X < 2B. Consequently, the variable distribution of fibre types within skeletal muscles is a major determinant of their large functional heterogeneity and plasticity. This presentation will mainly focus on the molecular and kinetics bases underlying the functional diversity among myosin isoforms.

Methods: 

Findings obtained by three main experimental approaches will be reported: (i) the analysis of the rates of acto-myosin dissociation by ATP and of ADP release from acto-myosin in solution by flash-photolysis; (ii) the analysis of step size and of time of attachment using single molecule mechanics, i.e. optical trap (OT); (iii) the analysis of the velocity of actin filaments propelled by pure myosin soforms at variable [ATP] and [ADP], and temperatures with "in vitro motility assays" (IVMA) approach.

Results: 

Collectively, the results indicate that the major determinant of the large variability of velocity among skeletal myosins is the rate at which ADP is released by the acto-myosin complex.

Conclusions: 

However, it will be suggested that the relative contribution of rate of acto-myosin dissociation by ATP and of the rate of ADP release in defining velocity is different in slow and fast myosins and varies with temperature.