Length-dependence of cross-bridge mediated activation of the cardiac thin filament

Length-dependent Ca2+ activation of the thin filament plays a critical role in the steep force-length relationship of cardiac muscle (Frank-Starling r elation). Recent evidence indicates that the increase in myofilament Ca2+ s ensitivity and Ca2+-troponin C affinity that occurs with increase in sarcom ere length results from a cooperative activation of the thin filament by at tached cross-bridges. At short sarcomere length the Ca2+ sensitivity is low er because the access of cross-bridges for actin is reduced. The aim of thi s study was to determine the length-dependence of myosin-mediated thin fila ment activation in skinned bovine ventricular muscle, as assayed by the gen eration of force with progressive reduction of MgATP concentration in the a bsence of Ca2+, If the interaction between myosin and actin is weaker at sh ort sarcomere length there should be a lower MgATP concentration needed to maintain the relaxed state. Contrary to expectation, the force-pMgATP relat ionship was not significantly influenced by change in sarcomere length. How ever this relationship became length-sensitive in the presence of phosphate analogs which stabilize weak-binding cross-bridges. We suggest Chat sarcom ere length modulates Ca2+ sensitivity by controlling the size of the popula tion of thin filament regulatory units in the weakly-bound state. (C) 2000 Academic Press.