Development of novel therapeutic options for treating heart failure targeting the myosin light chain

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A myosin molecule consists of two heavy chains and two pairs of light chains and converts chemical energy of ATP hydrolysis into mechanical work of muscle contraction. The light chains are located close to the heavy chain head domain which contains ATP- and actin-binding sites essential for the motor function. To study functional roles of the myosin light chains, we purified two cardiac myosins with identical heavy chain and different light chains and compared the motor function of these myosins using in vitro motility assay techniques, where mechanical interaction of actin and myosin was reconstituted in vitro. Although catalytic activity showed no difference, motor function of these myosin molecules showed remarkable difference : the myosin molecules with ventricular-type light chains generated higher average force compared to those with atrial-type light chains and had longer duration of force-generating interaction with actin, suggesting that the myosin light chains may play an important role in converting the chemical energy into mechanical work. The unique nature of the myosin light chain modifying force-generating ability of the molecule without changing ATP hydrolysis rate may provide a clue to novel treatment for heart failure augmenting contractile function without increasing ATP consumption and protecting cardiac muscles from deterioration in energy metabolism.