This study was undertaken to determine the impact of sarcomere length (SL) on the level of cooperative activation of the cardiac myofilament at physiological [Mg2+]. Active force development was measured in skinned rat cardiac trabeculae as a function of free [Ca2+] at five SLs (1.85–2.25 μm; 1 mM free [Mg2+]; 15°C). Only muscle preparations with minimal force rundown during the entire protocol were included in the analysis (average 7.2 ± 1.7%). Median SL was measured by on-line computer video micrometry and controlled within 0.01 μm. Care was taken to ensure a sufficient number of data points in the steep portion of the [Ca2+]-force relationship at every SL to allow for accurate fit of the data to a modified Hill equation. Multiple linear regression analysis of the fit parameters revealed that both maximum, Ca2+-saturated force and Ca2+sensitivity were a significant function of SL ( P < 0.001), whereas the level of cooperativity did not depend on SL ( P = 0.2). Further analysis of the [Ca2+]-force relationships revealed a marked asymmetry that, also, was not affected by SL ( P = 0.2–0.6). Finally, we found that the level of cooperativity in isolated skinned myocardium was comparable to that reported for intact, nonskinned myocardium. Our results suggest that an increase in SL induces an increase in the Ca2+ responsiveness of the cardiac sarcomere without affecting the level of cooperativity.
Cooperative activation of divergent pathways by LPAR1 and LPAR2 receptors in fibrotic signaling
