© 2000 American Heart Association, Inc.
Cellular Biology |
Strongly Binding Myosin Crossbridges Regulate Loaded Shortening and Power Output in Cardiac Myocytes
From the Department of Physiology (K.S.M.), University of Missouri School of Medicine, Columbia, Mo, and Department of Physiology (R.L.M.), University of Wisconsin Medical School, Madison, Wis.
Correspondence to Kerry S. McDonald, PhD, Department of Physiology, School of Medicine, University of Missouri, MA415 Medical Sciences Building, Columbia, MO 65212. E-mail mcdonaldks{at}missouri.edu \ © 2000 American Heart Association, Inc.
Abstract—This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during varying levels of Ca2+ activation. Lowering the [Ca2+] slowed shortening velocities, decreased relative power output, and increased the curvature of length traces. We tested the hypothesis that Ca2+ activation dependence of loaded shortening is determined primarily by strongly binding crossbridges or by [Ca2+] per se, which was done by measuring loaded shortening before and after addition of N-ethylmaleimide–conjugated myosin subfragment-1 (NEM-S1), a strongly binding myosin analogue that cooperatively enhances thin filament activation. At fixed [Ca2+], NEM-S1 reduced the curvature of length traces and sped loaded shortening velocities. Even when [Ca2+] was adjusted so that force was equal with and without NEM-S1, myocyte shortening was faster and exhibited less curvature with NEM-S1. In the presence of NEM-S1, peak relative power output was also significantly greater during activations either at the same [Ca2+] or when [Ca2+] was adjusted to achieve the same force. Consequently, NEM-S1 eliminated any Ca2+ dependence of relative power output that is normally observed in cardiac myocytes. These results indicate that strongly binding crossbridges play a significant role in determining loaded shortening and power output and suggest that previously observed Ca2+ dependence of power output is mediated by alterations in numbers of crossbridges bound to the thin filament.
Key Words: cardiac myocytes • power output • myosin
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