The effect of myofilament compliance on kinetics of force generation by myosin motors in muscle.
We use the inhibitor of isometric force of skeletal muscle N-benzyl-p-toluene sulfonamide (BTS) to decrease, in a dose dependent way, the number of myosin motors attached to actin during the steady isometric contraction of single fibers from frog skeletal muscle (4 degrees C, 2.1 microm sarcomere length). In this way we can reduce the strain in the myofilament compliance during the isometric tetanus (T(0)) from 3.54 nm in the control solution (T(0,NR)) to approximately 0.5 nm in 1 microM BTS, where T(0) is reduced to approximately 0.15 T(0,NR). The quick force recovery after a step release (1-3 nm per half-sarcomere) becomes faster with the increase of BTS concentration and the decrease of T(0). The simulation of quick force recovery with a multistate model of force generation, that adapts Huxley and Simmons model to account for both the high stiffness of the myosin motor (approximately 3 pN/nm) and the myofilament compliance, shows that the increase in the rate of quick force recovery by BTS is explained by the reduced strain in the myofilaments, consequent to the decrease in half-sarcomere force. The model estimates that i), for the same half-sarcomere release the state transition kinetics in the myosin motor are five times faster in the absence of filament compliance than in the control; and ii), the rate of force recovery from zero to T(0) is approximately 6000/s in the absence of filament compliance.
Linari
M
M
Laboratorio di Fisiologia, Dipartimento di Biologia Evoluzionistica, Università di Firenze, Sesto Fiorentino, Firenze, Italy.
Piazzesi
G
G
Lombardi
V
V
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000199:Actins / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D011896:Rana temporaria; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology
D000199:Actins; C444880:N-benzyl-p-toluene sulfonamide; D013449:Sulfonamides; D014050:Toluene; D009218:Myosins