Effect of ionic strength on length-dependent Ca2+ activation in skinned cardiac muscle

The length-dependence of myofilament Ca2+ sensitivity is considered to be a n important component of the steep force-length relationship in cardiac mus cle (Frank-Starling relation). Recent studies suggest that Ca2+ sensitivity is a function of the number of strong-binding cross-bridge interactions fo rmed at a given sarcomere length. However, the length-dependent step in the thin filament activation process is still unknown, This study was designed to test the hypothesis that sarcomere length influences the transition of the thin filament from the unattached (blocked) state to the weakly bound ( closed) state, This hypothesis was tested by determining the length-depende nce of Ca2+ sensitivity as a function of ionic strength in skinned bovine v entricular muscle. Previous studies have shown that reduction in ionic stre ngth below a critical level, in the absence of Ca2+, shifts the thin filame nt to the closed state. In this study normal Ca2+ regulation was maintained at low ionic strength but the length-dependence of Ca2+ sensitivity and th e length-dependence of Ca2+ binding were eliminated, These results are cons istent with the hypothesis that the transition from the blocked to the clos ed state is a function of filament geometry as well as Ca2+ and ionic stren gth, (C) 1999 Academic Press.