| First Author | Ford SJ | Year | 2013 |
| Journal | Arch Biochem Biophys | Volume | 535 |
| Issue | 1 | Pages | 3-13 |
| PubMed ID | 23111184 | Mgi Jnum | J:205621 |
| Mgi Id | MGI:5545942 | Doi | 10.1016/j.abb.2012.10.011 |
| Citation | Ford SJ, et al. (2013) Length-dependent effects on cardiac contractile dynamics are different in cardiac muscle containing alpha- or beta-myosin heavy chain. Arch Biochem Biophys 535(1):3-13 |
| abstractText | 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, alpha-myosin heavy chain (MHC) isoform, whereas slower kinetics are imparted on XBs comprised of the slow, beta-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 beta-MHC were more sensitive to such length-dependent effects than those of alpha-MHC. We studied the SL effects on mechanical properties of demembranated muscle fibers from normal and propylthiouracil-treated mouse hearts, which expressed predominantly alpha-MHC or beta-MHC, respectively. Interestingly, XB detachment kinetics were more length-sensitive in beta-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 beta-MHC fibers. This phenomenon is attributed to a greater cooperative/allosteric mechanism in beta-MHC fibers, as estimated by model parameter gamma. 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 beta-MHC. |
