Myofilament kinetics in isometric twitch dynamics

To better understand the relationship between kinetic processes of contraction and the dynamic features of an isometric twitch, studies were conducted using a mathematical model that included: (1) kinetics of cross bridge (XB) cycling; (2) kinetics of thin filament regulatory processes; (3) serial and feedback interactions between these two kinetic processes; and (4) time course of calcium activation. Isometric twitch wave forms were predicted, morphometric features of the predicted twitch wave form were evaluated, and sensitivities of wave form morphometric features to model kinetic parameters were assessed. Initially, the impulse response of the XB cycle alone was analyzed with the findings that dynamic constants of the twitch transient were much faster than turnover number of steady-state XB cycling, and, although speed and duration of the twitch wave form were sensitive to XB cycle kinetic constants. parameters of wave shape were not. When thin filament regulatory unit (RU) kinetics were added to XB cycle kinetics, the system impulse response was slowed with only little effect on wave shape. When cooperative neighbor interactions between RU and XB were added, twitch wave shape (as well as amplitude, speed and duration) proved to be sensitive to variation in cooperativity. Importantly, persistence and shape of the falling phase could be strongly modified. When kinetic coefficients of XB attachment were made to depend on sarcomere length, changes in wave shape occurred that did not occur when only sliding filament mechanisms were operative. Indeed, the force-length relationship proved to be highly sensitive to length-dependent XB attachment in combination with cooperative interactions. These model findings are the basis of hypotheses for the role of specific kinetic events of contraction in generating twitch wave form features.