title: Length-dependent effects on cardiac contractile dynamics are different in cardiac muscle containing α- or β-myosin heavy chain.
abstract: Actomyosin crossbridges (XBs) are the fundamental source of force generation and pressure development in the myocardium. Faster kinetics are imparted on XBs comprised of the fast, α-myosin heavy chain (MHC) isoform, whereas slower kinetics are imparted on XBs comprised of the slow, β-MHC isoform. Other factors, such as sarcomere length (SL), influence XB formation, presumably acting through allosteric effects on the kinetics that regulate the XB cycle. We sought to determine whether the slower XB kinetics of β-MHC were more sensitive to such length-dependent effects than those of α-MHC. We studied the SL effects on mechanical properties of demembranated muscle fibers from normal and propylthiouracil-treated mouse hearts, which expressed predominantly α-MHC or β-MHC, respectively. Interestingly, XB detachment kinetics were more length-sensitive in β-MHC fibers, as estimated by tension cost and XB detachment rate constant (c), and as inferred by ktr. The nonlinearity in force responses to various-amplitude step-like changes in muscle length was more pronounced in β-MHC fibers. This phenomenon is attributed to a greater cooperative/allosteric mechanism in β-MHC fibers, as estimated by model parameter γ. These data suggest a mechanism whereby greater cooperative/allosteric effects impart an enhanced length-sensitivity of XB cycling kinetics in fibers containing the slower cycling β-MHC.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology VCAPP, Washington State University, 205 Wegner Hall, Pullman, WA 99164, United States. sford@vetmed.wsu.edu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ford
authors.forename: Murali
authors.initials: M
authors.lastname: Chandra
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction; D009129:Muscle Tonus; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism*; D010766:Phosphorylation; D011441:Propylthiouracil / Q000494:pharmacology; D012518:Sarcomeres / Q000378:metabolism; D024723:Ventricular Myosins / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; C551613:Myh7 protein, mouse; D011441:Propylthiouracil; D000255:Adenosine Triphosphate; D000205:Actomyosin; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains; D002118:Calcium