M.Sc Thesis

M.Sc StudentTchaychian Oren
SubjectThe Effect of the Sarcomere Shortening Velocity on the
Rate of Energy Consumption, Based on Coupling
Cross-Bridge Cycling with Calcium
Kinetics: Theoretical Analysis
DepartmentDepartment of Biomedical Engineering
Supervisor ASSOCIATE PROF. Amir Landesberg


Energy liberation rate (Ė) during steady muscle shortening is a monotonic increasing or biphasic function of the shortening velocity (V). The study examines three plausible hypotheses for explaining the biphasic Ė-V relationship (ĖVR): (i) The cross-bridge (XB) turnover rate from non force-generating (weak) to force-generating (strong) conformation decreases as V increases; (ii) XB kinetics is determined by the number of strong XBs (XB-XB cooperativity); (iii) The affinity of troponin for calcium is modulated by the number of strong XBs (XB-Ca cooperativity). The relative role of the various energy regulating mechanisms is not well defined. The hypotheses were tested by coupling calcium kinetics with XB cycling. All three hypotheses yield identical steady-state characteristics: (i) Hyperbolic Force-Velocity relationship; (ii) Quasi-linear Stiffness-Force relationship; and (iii) Biphasic ĖVR, where Ė declines at high V due to decrease in the number of cycling XBs or in the weak-to-strong transition rate. The hypotheses differ in the ability to describe the existence of both monotonic and biphasic ĖVRs and in the effect of [Ca2+]i on the ĖVR peak. Monotonic and biphasic ĖVRs with a shift in ĖVR peak to higher velocity at higher [Ca2+]i are obtained only by XB-Ca Cooperativity. XB-XB cooperativity provides only biphasic ĖVRs. A direct effect of V on XB kinetics predicts that ĖVR-peak is obtained at the same velocity independently of [Ca2+]i. The study predicts that measuring the dependence of the ĖVR on [Ca2+]i allows to test the hypotheses and to identify the dominant energy regulating mechanism. The established XB-XB and XB-Ca mechanisms provide alternative explanations to the various reported ĖVRs.