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Am J Physiol Heart Circ Physiol 279: H1355-H1364, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 3, H1355-H1364, September 2000

Myosin light chain replacement in the heart

Atsushi Sanbe1, James Gulick1, Eric Hayes2, David Warshaw2, Hanna Osinska1, Chi-Bew Chan1, Raisa Klevitsky1, and Jeffrey Robbins1

1 The Children's Hospital Research Foundation, Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio 45229-3039; and 2 Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont 05405-0068

Myosin-actin cross-bridge kinetics are an important determinant for cardiac systolic and diastolic function. We compared the effects of myosin light chain substitutions on the ability of the fibers to contract in response to calcium and in their ability to produce power. Transgenesis was used to effect essentially complete replacement of the target contractile protein isoform specifically in the heart. Atrial and ventricular fibers derived from the various transgenic (TG) lines were skinned, and the force-velocity relationships, unloaded shortening velocities, and Ca2+-stimulated Mg2+-ATPase activities were determined. Replacement with an ectopic isoform resulted in significant changes in cross-bridge cycling kinetics but without any overt effects on morbidity or mortality. To confirm that this result was not light chain specific, a modified alpha -myosin heavy chain isoform that resulted in significant changes in force development was also engineered. The animals appeared healthy and have normal lifespans, and the changes in force development did not result in significant remodeling or overt hypertrophy. We conclude that myosin light chains can control aspects of cross-bridge cycling and alter force development. The myosin heavy chain data also show that changes in the kinetics of force development and power output do not necessarily lead to activation of the hypertrophic response or significant cardiac remodeling.

transgenesis; muscle; adenosinetriphosphatase; cross-bridge action


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