Sarcomere length versus interfilament spacing as determinants of cardiac myofilament Ca2+ sensitivity and Ca2+...

The Ca2+ sensitivity of skinned cardiac muscle can be increased by either an increase in sarcomere length or osmotic compression of the myofilament lattice. The length-dependent change in Ca2+ sensitivity is considered to be an important component of the steep force-length relation along the ascending limb of the force-length curve (Frank-Starling relation). Since an increase in sarcomere length is accompanied by a reduction in the spacing between myosin and actin filaments it is not clear whether length-dependent changes in Ca2+ sensitivity are related to changes in sarcomere length, interfilament spacing or some combination of both. To obtain quantitative information on the relative contributions of these two parameters to the determination of Ca2+ sensitivity skinned bovine cardiac muscle bundles of varying sarcomere lengths (1.7-2.3 microns) were exposed to varying concentrations (0-5%) of Dextran T-500. Measurements were made of changes in muscle width in response to Dextran T-500 addition and both force-pCa curves and bound Ca(2+)-pCa curves were obtained as a function of sarcomere length and lattice compression. From the data obtained it was possible to compare Ca2+ sensitivity and Ca(2+)-troponin C affinity at different sarcomere lengths under conditions of changing interfilament spacing and constant interfilament spacing. Both Ca2+ sensitivity and Ca2+ binding correlated more closely with change in interfilament spacing than with change in sarcomere length. These results suggest that length-dependent force generation in cardiac muscle is based primarily on length-dependent changes in the separation between myosin and actin filaments.