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Articles in PresS, published online ahead of print November 14, 2001
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00667.2001
Submitted on July 30, 2001
Accepted on December 31, 1969
1 Department of Physiology and Biophysics and Cardiovascular Sciences Program, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: pdetombe{at}uic.edu.
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 SL's (1.85-2.25 µm; 1 mM free [Mg2+]; 15 C). Only muscle preparations with minimal force run-down 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, calcium saturated force and calcium 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, non-skinned myocardium. Our results suggest that an increase in sarcomere length induces an increase in the calcium responsiveness of the cardiac sarcomere without affecting the level of cooperativity.
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