title: Size and speed of the working stroke of cardiac myosin in situ.
abstract: 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.
authors.affiliation: Laboratory of Physiology, Department of Biology, Università di Firenze, 50019 Sesto Fiorentino, Florence, Italy;
authors.forename: Marco
authors.initials: M
authors.lastname: Caremani
authors.affiliation: Laboratory of Physiology, Department of Biology, Università di Firenze, 50019 Sesto Fiorentino, Florence, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Pinzauti
authors.affiliation: Laboratory of Physiology, Department of Biology, Università di Firenze, 50019 Sesto Fiorentino, Florence, Italy;
authors.forename: Massimo
authors.initials: M
authors.lastname: Reconditi
authors.affiliation: Laboratory of Physiology, Department of Biology, Università di Firenze, 50019 Sesto Fiorentino, Florence, Italy;
authors.forename: Gabriella
authors.initials: G
authors.lastname: Piazzesi
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, 1081 HV Amsterdam, The Netherlands; Department of Physics and Astronomy, Faculty of Science, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Stienen
authors.affiliation: Laboratory of Physiology, Department of Biology, Università di Firenze, 50019 Sesto Fiorentino, Florence, Italy; vincenzo.lombardi@unifi.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lombardi
authors.affiliation: Laboratory of Physiology, Department of Biology, Università di Firenze, 50019 Sesto Fiorentino, Florence, Italy;
authors.forename: Marco
authors.initials: M
authors.lastname: Linari
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D024722:Cardiac Myosins / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D020409:Molecular Motor Proteins / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000502:physiology; D024723:Ventricular Myosins / Q000502:physiology
chemical_list: D020409:Molecular Motor Proteins; D024722:Cardiac Myosins; D024723:Ventricular Myosins; D002118:Calcium
keywords: cardiac myosin; heart mechanics; myosin working stroke