Molecular control of myocardial mechanics and energetics: the chemo-mechanical conversion.
Energy consumption in the cardiac muscle is characterized by two basic phenomena: 1) The well known linear relationship between energy consumption by the sarcomere and the mechanical energy it generates, and 2) the ability to modulate the generated mechanical energy and energy consumption to the various loading conditions, as is manifested by the Frank-Starling Law and the Fenn effect. These basic phenomena are analyzed here based on coupling calcium kinetics with crossbridge (Xb) cycling. Our previous studies established the existence of two feedback mechanism: 1) a positive feedback mechanism, the cooperativity, whereby the affinity of the troponin for calcium, and hence Xb and actomyosin-ATPase recruitment, depends on the number of force generating Xbs, and 2) a mechanical feedback, whereby the filaments shortening velocity, or the Xb strain rate, determines the rate of Xb turnover from the strong to the weak conformation. The cooperativity mechanism determines the force-length relationship (FLR) and the related Frank-Starling Law. It also provides the basis for the regulation of energy consumption and the ability of the muscle to adapt its energy consumption to the loading conditions. The mechanical feedback regulates the shortening velocity and provides the analytical solution for the experimentally derived Hill's equation for the force-velocity relationship (FVR). The mechanical feedback regulates the generated power and provides the linear relationship between energy consumption and the generated mechanical energy, i.e., the external work done and the liberated heat. Thus, the two feedback mechanisms that regulate sarcomere dynamics, and determine the FLR and FVR, also regulate the energy consumption and the mechanical energy generated by the muscle.
Landesberg
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Julius Silver Institute, Department of Biomedical Engineering, Technion-IIT, Haifa, Israel.
D000818:Animals; D001696:Biomechanical Phenomena; D004734:Energy Metabolism; D005246:Feedback; D006801:Humans; D008433:Mathematics; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*