Is the cross-bridge stiffness proportional to tension during muscle fiber activation?
The cross-bridge stiffness can be used to estimate the number of S1 that are bound to actin during contraction, which is a critical parameter for elucidating the fundamental mechanism of the myosin motor. At present, the development of active tension and the increase in muscle stiffness due to S1 binding to actin are thought to be linearly related to the number of cross-bridges formed upon activation. The nonlinearity of total stiffness with respect to active force is thought to arise from the contribution of actin and myosin filament stiffness to total sarcomere elasticity. In this work, we reexamined the relation of total stiffness to tension during activation and during exposure to N-benzyl-p-toluene sulphonamide, an inhibitor of cross-bridge formation. In addition to filament and cross-bridge elasticity, our findings are best accounted for by the inclusion of an extra elasticity in parallel with the cross-bridges, which is formed upon activation but is insensitive to the subsequent level of cross-bridge formation. By analyzing the rupture tension of the muscle (an independent measure of cross-bridge formation) at different levels of activation, we found that this additional elasticity could be explained as the stiffness of a population of no-force-generating cross-bridges. These findings call into question the assumption that active force development can be taken as directly proportional to the cross-bridge number.
Colombini
Barbara
B
Dipartimento di Scienze Fisiologiche and Istituto Interuniversitario di Miologia, Università degli Studi di Firenze, Firenze, Italy.
Nocella
Marta
M
Bagni
M Angela
MA
Griffiths
Peter J
PJ
Cecchi
Giovanni
G
D000199:Actins / Q000378:metabolism*; D000818:Animals; D004548:Elasticity; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D010507:Periodicity; D011893:Rana esculenta; D000077331:Ringer's Solution; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology
D000199:Actins; D007552:Isotonic Solutions; C444880:N-benzyl-p-toluene sulfonamide; D013449:Sulfonamides; D014050:Toluene; D000077331:Ringer's Solution; D009218:Myosins