Regulation of myosin light chain phosphatase and myofilament Ca2+ sensitivity in smooth muscle: a tale of research on smooth muscle contraction.

Contraction of both striated and smooth muscles is regulated by intracellular Ca2+ signals. The mechanisms of contraction following the Ca2+ signal are significantly different between striated and smooth muscles. The Ca2+-dependent reversible phosphorylation of the 20 kDa myosin light chain plays an essential role in regulating smooth muscle contraction. The phosphorylation theory of smooth muscle contraction was proposed in the mid-1970s. In the late 1980s, quantitative evaluation of cytosolic Ca2+ concentrations and contraction revealed that the contraction was not always associated with changes in cytosolic Ca2+ concentrations. G protein-coupled receptor agonists generally produce a greater contraction at a certain level of Ca2+ than membrane depolarization. Consequently, the concept of dual regulation, in which smooth muscle contraction is regulated by not only Ca2+ signals but also myofilament Ca2+ sensitivity, was established. The identification of smooth muscle myosin light chain phosphatase in the early 1990s greatly facilitated the understanding of the molecular mechanisms regulating myofilament Ca2+ sensitivity over the following 10 years. The overall picture of the mechanisms of smooth muscle contraction became clearer by the early 2000s. Smooth muscle research is ready to open a new horizon of translational research aimed at precision medicine for smooth muscle diseases, such as hypertension, asthma, and dyspepsia. The present review article overviews the history of research on smooth muscle contraction and summarizes the current understanding of the mechanisms of smooth muscle contraction, focusing on the regulation of myosin light chain phosphatase and myofilament Ca2+ sensitivity.