In rat ventricular trabeculae, reducing load increased the size and speed of the myosin working stroke from ~3 nm and 1,000 s(-1) to ~8 nm and 6,000 s(-1), independent of sarcomere length and calcium.
Length- and Ca(2+)-dependent increases in cardiac power are driven by the modulation of the number of active myosin motors rather than changes in the size or speed of individual motor working strokes.
The power in the myocardium sarcomere is generated by two bipolar arrays of the motor protein cardiac myosin II extending from the thick filament and pulling the thin, actin-containing filaments from the opposite sides of the sarcomere. Despite the interest in the definition of myosin-based cardiomyopathies, no study has yet been able to determine the mechanokinetic properties of this motor protein in situ. Sarcomere-level mechanics recorded by a striation follower is used in electrically stimulated intact ventricular trabeculae from the rat heart to determine the isotonic velocity transient following a stepwise reduction in force from the isometric peak force TP to a value T(0.8-0.2 TP). The size and the speed of the early rapid shortening (the isotonic working stroke) increase by reducing T from ∼3 nm per half-sarcomere (hs) and 1,000 s(-1) at high load to ∼8 nm⋅hs(-1) and 6,000 s(-1) at low load. Increases in sarcomere length (1.9-2.2 μm) and external Ca(2+)o (1-2.5 mM), which produce an increase of TP, do not affect the dependence on T, normalized for TP, of the size and speed of the working stroke. Thus, length- and Ca(2+)-dependent increase of TP and power in the heart can solely be explained by modulation of the number of myosin motors, an emergent property of their array arrangement. The motor working stroke is similar to that of skeletal muscle myosin, whereas its speed is about three times slower. A new powerful tool for investigations and therapies of myosin-based cardiomyopathies is now within our reach.
Caremani et al. (Wed,) conducted a other in Myosin-based cardiomyopathies (context). Stepwise reduction in force (load) vs. High load / isometric peak force was evaluated on Size and speed of the early rapid shortening (isotonic working stroke). In rat ventricular trabeculae, reducing load increased the size and speed of the myosin working stroke from ~3 nm and 1,000 s(-1) to ~8 nm and 6,000 s(-1), independent of sarcomere length and calcium.