Length-dependence of cross-bridge mediated activation of the cardiac thin filament.
Length-dependent Ca(2+)activation of the thin filament plays a critical role in the steep force-length relationship of cardiac muscle (Frank-Starling relation). Recent evidence indicates that the increase in myofilament Ca(2+)sensitivity and Ca(2+)-troponin C affinity that occurs with increase in sarcomere length results from a cooperative activation of the thin filament by attached cross-bridges. At short sarcomere length the Ca(2+)sensitivity is lower because the access of cross-bridges for actin is reduced. The aim of this study was to determine the length-dependence of myosin-mediated thin filament activation in skinned bovine ventricular muscle, as assayed by the generation of force with progressive reduction of MgATP concentration in the absence of Ca(2+). If the interaction between myosin and actin is weaker at short sarcomere length there should be a lower MgATP concentration needed to maintain the relaxed state. Contrary to expectation, the force-pMgATP relationship was not significantly influenced by change in sarcomere length. However this relationship became length-sensitive in the presence of phosphate analogs which stabilize weak-binding cross-bridges. We suggest that sarcomere length modulates Ca(2+)sensitivity by controlling the size of the population of thin filament regulatory units in the weakly-bound state.
Smith
S H
SH
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Fuchs
F
F
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D006352:Heart Ventricles / Q000378:metabolism*; D012518:Sarcomeres / Q000502:physiology*; D019209:Troponin C / Q000378:metabolism; D016276:Ventricular Function
D019209:Troponin C; D000255:Adenosine Triphosphate; D002118:Calcium