Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses.
Length-dependent steady-state and dynamic responses of five models of isometric force generation in cardiac myofilaments were compared with similar experimental data from the literature. The models were constructed by assuming different subsets of three putative cooperative mechanisms. Cooperative mechanism 1 holds that cross-bridge binding increases the affinity of troponin for Ca2+. In the models, cooperative mechanism 1 can produce steep force-Ca2+ (F-Ca) relations, but apparent cooperativity is highest at midlevel Ca2+ concentrations. During twitches, cooperative mechanism 1 has the effect of increasing latency to peak as the magnitude of force increases, an effect not seen experimentally. Cooperative mechanism 2 holds that the binding of a cross bridge increases the rate of formation of neighboring cross bridges and that multiple cross bridges can maintain activation of the thin filament in the absence of Ca2+. Only cooperative mechanism 2 can produce sarcomere length (SL)-dependent prolongation of twitches, but this mechanism has little effect on steady-state F-Ca relations. Cooperativity mechanism 3 is designed to simulate end-to-end interactions between adjacent troponin and tropomyosin. This mechanism can produce steep F-Ca relations with appropriate SL-dependent changes in Ca2+ sensitivity. With the assumption that tropomyosin shifting is faster than cross-bridge cycling, cooperative mechanism 3 produces twitches where latency to peak is independent of the magnitude of force, as seen experimentally.
D008841:Actin Cytoskeleton / Q000502:physiology; D002118:Calcium / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology*; D008955:Models, Cardiovascular; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D014336:Troponin / Q000502:physiology