EFFECTS OF TOTAL REPLACEMENT OF ATRIAL MYOSIN LIGHT CHAIN-2 WITH THE VENTRICULAR ISOFORM IN ATRIAL MYOCYTES OF TRANSGENIC MICE

Background-In contrast to their well-known and critical role in excita tion-contraction coupling of vascular smooth muscle, the effects of th e myosin light chains on cardiomyocyte mechanics are poorly understood . Accordingly, we designed the present experiment to define the cardia c chamber-specific functional effects of the ventricular isoform of th e regulatory myosin light chain (MLC2v).Methods and Results-Postnatal transgenic cardiac-specific overexpression of MLC2v was achieved by us e of the alpha-myosin heavy chain promoter. Enzymatically disaggregate d atrial and ventricular mouse myocytes were field-stimulated at multi ple frequencies, and mechanical properties and calcium kinetics were s tudied by use of video edge detection and FURA 2-AM, respectively. MLC 2v overexpression resulted in complete replacement of the atrial with the ventricular isoform of the regulatory myosin light chain at the st eady-state mRNA and protein levels in the atria of transgenic mice. Me chanical 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. Conclusion s-MLC2v modulates chamber-specific contractility by enhanced calcium s ensitivity and/or improved cross-bridge cycling of the thin and thick filaments of the cardiomyocyte.