Discovery of the regulatory role of calcium ion in muscle contraction and relaxation: Setsuro Ebashi and the international emergence of Japanese muscle research

In the early 1950s Setsuro Ebashi was a graduate student at Tokyo University studying the biochemical models of muscle contraction. The muscle components in these models contracted in the presence of ATP, but what caught his attention was that the components did not relax when ATP was exhausted. Ebashi decided in 1952 to attempt to elucidate the mechanism of muscle relaxation using these models. This decision started a journey that would lead him to be the first to propose the calcium concept of muscle contraction and relaxation in 1961. It was an unpopular theory with biochemists who refused to accept that anything as simple as an inorganic ion, Ca2+, could control anything as important as muscle contraction. Ebashi was convinced that he was correct. He proceeded to show that micromolar concentrations of Ca2+ activated contraction. In 1961 he discovered the particulate nature of the ATP-dependent relaxing factor (the sarcoplasmic reticulum) and determined that it acted by binding Ca2+. Most notably, in 1966 he discovered troponin, the Ca2+ receptor in muscle, which mediated Ca2+ control of contraction. Ebashi's discoveries were considered the most important in the muscle field since the 1950s. Ebashi had to overcome the doubt of the scientific community. This story is one of great scientific achievement against great odds that marked the emergence of Japanese muscle research onto the international scientific stage.NEW & NOTEWORTHY Setsuro Ebashi proposed the calcium concept of muscle contraction and relaxation in 1961. It was a very unpopular theory. He showed that Ca2+ activated contraction and that the sarcoplasmic reticulum caused relaxation by binding Ca2+ in an ATP-dependent manner. Most notably, he discovered the receptor that mediated Ca2+ control of contraction and named it "troponin." Ebashi's discoveries are considered to be the most important in the muscle field since the 1950s.