M.Sc Student | Oren Tchaychian |
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Subject | The Effect of the Sarcomere Shortening Velocity on the Rate of Energy Consumption, Based on Coupling Cross-Bridge Cycling with Calcium Kinetics: Theoretical Analysis |

Department | Department of Biomedical Engineering |

Supervisor | Professor Landesberg Amir |

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 *ĖVR*s
and in the effect of [Ca^{2+}]_{i} on the* ĖVR* peak.
Monotonic and biphasic *ĖVRs* with a shift in *ĖVR* peak to
higher velocity at higher [Ca^{2+}]_{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 [Ca^{2+}]_{i}.
The study predicts that measuring the dependence of the *ĖVR* on [Ca^{2+}]_{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*.