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(Circulation. 1998;97:1508-1513.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Effects of Total Replacement of Atrial Myosin Light Chain-2 With the Ventricular Isoform in Atrial Myocytes of Transgenic Mice

Corinn M. Pawloski-Dahm, PhD; Guojie Song, MD, PhD; Darryl L. Kirkpatrick, BS; Joe Palermo, PhD; James Gulick, MS; Gerald W. Dorn, II, MD; Jeffrey Robbins, PhD; ; Richard A. Walsh, MD

From the Department of Medicine, Division of Cardiology (C.M.P.-D., G.S., D.L.K., G.W.D., R.A.W.), and Department of Pediatrics, Division of Molecular Cardiovascular Biology (J.P., J.G., J.R.), University of Cincinnati Medical Center, 231 Bethesda Ave, Cincinnati, Ohio.

Background—In contrast to their well-known and critical role in excitation-contraction coupling of vascular smooth muscle, the effects of the myosin light chains on cardiomyocyte mechanics are poorly understood. Accordingly, we designed the present experiment to define the cardiac chamber–specific functional effects of the ventricular isoform of the regulatory myosin light chain (MLC2v).

Methods and Results—Postnatal transgenic cardiac-specific overexpression of MLC2v was achieved by use of the -myosin heavy chain promoter. Enzymatically disaggregated atrial and ventricular mouse myocytes were field-stimulated at multiple frequencies, and mechanical properties and calcium kinetics were studied by use of video edge detection and FURA 2-AM, respectively. MLC2v overexpression resulted in complete replacement of the atrial with the ventricular isoform of the regulatory myosin light chain at the steady-state mRNA and protein levels in the atria of transgenic mice. Mechanical properties of transgenic atrial myocytes were enhanced to the level of ventricular myocytes of control animals in association with modest decreases in the amplitude of the calcium transient.

Conclusions—MLC2v modulates chamber-specific contractility by enhanced calcium sensitivity and/or improved cross-bridge cycling of the thin and thick filaments of the cardiomyocyte.

Key Words: genes • myocytes • myosin

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