טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentLevy Carmit
SubjectRegulation of Cross-Bridge Recruitment in the Cardiac
Muscle: Identification of the Cooperativity
Mechanism
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Amir Landesberg


Abstract

The existence of a cooperativity mechanism that regulates cross-bridge (XB) recruitment affects the force response to sarcomere length (SL) oscillations. The study examined the force responses to large (100nm/sarcomere) SL oscillations, during steady tetanus contractions, at different conditions (SL, frequency and extra-cellular calcium concentrations [Ca2+]0). Trabeculae (n=24) were obtained from rat right ventricles and were tetanized using cyclopiazonic acid (K-H, 250C). SL was measured by laser diffraction techniques and force by silicon strain gauge. The dynamic stiffness, an index for the number of strong XBs was measured by superimposing additional fast and small length oscillations (50Hz, 2.25nm). The force responses lagged the SL oscillations (112±41msec at 1 Hz) yielding counter clockwise hysteresis between the force and the SL, at frequencies smaller than 4Hz and short SL (<1.9 5mm). At higher frequencies (>4Hz, SL<1.9 5mm) the force preceded the SL yielding clockwise hysteresis (n=7). Similar hystereses were obtained in the force-SL and stiffness-SL planes. For constant frequency (1Hz) and [Ca2+]0 (6mM), the phase between the force and SL responses was length dependent; the force lagged the SL changes at short SL (SL<1.9 5mm) and preceded the SL at longer SL (n=6). Interestingly, for constant SL, the phase decreased with increasing the [Ca2+]0 (n=6). However, the phases were identical and length independent when the mean force during the oscillations was kept constant, by using different pairs of [Ca2+]0 and SLs (n=6). We conclude that the cooperativity mechanism is determined by the number of strong XBs. The XBs are the myocyte sensors that modulate XB recruitment and energy consumption in response to load changes.