title: The cross-bridge dynamics is determined by two length-independent kinetics: Implications on muscle economy and Frank-Starling Law.
abstract: The cellular mechanisms underlying the Frank-Starling Law of the heart and the skeletal muscle force-length relationship are not clear. This study tested the effects of sarcomere length (SL) on the average force per cross-bridge and on the rate of cross-bridge cycling in intact rat cardiac trabeculae (n=9). SL was measured by laser diffraction and controlled with a fast servomotor to produce varying initial SLs. Tetanic contractions were induced by addition of cyclopiazonic acid, to maintain a constant activation. Stress decline and redevelopment in response to identical ramp shortenings, starting at various initial SLs, was analyzed. Both stress decline and redevelopment responses revealed two distinct kinetics: a fast and a slower phase. The duration of the rapid phases (4.2 ± 0.1 msec) was SL-independent. The second slower phase depicted a linear dependence of the rate of stress change on the instantaneous stress level. Identical slopes (70.5 ± 1.6 [1/s], p=0.33) were obtained during ramp shortening at all initial SLs, indicating that the force per cross-bridge and cross-bridge cycling kinetics are length-independent. A decrease in the slope at longer SLs was obtained during stress redevelopment, due to internal shortening. The first phase is attributed to rapid changes in the average force per cross-bridge. The second phase is ascribed to both cross-bridge cycling between its strong and weak conformations and to changes in the number of strong cross-bridges. Cross-bridge cycling kinetics and muscle economy are length-independent and the Frank-Starling Law cannot be attributed to changes in the force per cross-bridge or in the single cross-bridge cycling rates.
authors.affiliation: Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Daria
authors.initials: D
authors.lastname: Amiad Pavlov
authors.affiliation: Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel. Electronic address: amir@bm.technion.ac.il.
authors.forename: Amir
authors.initials: A
authors.lastname: Landesberg
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D006352:Heart Ventricles / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D054792:Muscle, Striated / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012518:Sarcomeres / Q000187:drug effects* / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D007211:Indoles; C000543:cyclopiazonic acid
keywords: Cross-bridge cycling; Force redevelopment; Force-length relationship; Frank–Starling law; Muscle contraction; Muscle economy