The Process of Muscular Contraction

ACOMPREHENSION of the ultimate nature of muscular contraction is of . great importance to the cardiologist. In view of the rapid and highly specialized progress in the study of myosin, actin and adenosine triphosphate as tha agents of contractile activity in various types of muscle, it may be desirable to give a brief orientation as to what this progress means. What are the main trends in its development? What does the evidence consist of? What conclusions have been reached? How do the new facts connect with other phases of metabolism and function? Most work in this field has been performed with substances derived from skeletal muscle. Anyone desiring to investigate the same problems for the myocardium will meet peculiar difficulties in regard to low yield or abnormal behavior of the material. This is due to our lack of knowledge and experience in cardiac biochemistry, it does not necessarily indicate that these two kinds of muscle are fundamentally different. To say, for example, that the amount of myosin in the heart is only one-twentieth of the total protein, means only that one has not yet learned to obtain it quantitatively. All muscular activity relies, eventually, on the consumption of oxygen. This does not mean that the contraction process itself is of an aerobic nature; indeed, many kinds of skeletal muscle can work anaerobically (through glycolysis) for a considerable time. The purpose of respiration, and of glycolysis, is to synthesize so-called energy-rich phosphate compounds, two of which occur in muscular tissues in marked concentration: adenosine triphosphate (ATP) and phosphocreatine (PC). The former substance is the immediate energy donor for all cellular processes. It occurs in mammalian muscles, including the heart, in the rather constant concentration of about 5 IXM. per gram fresh tissue. Phosphocreatine occurs in more varying amounts; in typical skeletal muscles it may exceed the adenosine triphosphate about four-fold, but in the heart there is considerably less than that. Phosphocreatine can transfer its phosphate group to adenosine diphosphate (ADP), thus turning it into adenosine triphosphate. In this sense, phosphocreatine acts as a reserve of adenosine triphosphate, but it may well have a more fundamental function in connection with relaxation or diastole. Adenosine triphosphate makes its energy available when it is dephosphorylated to adenosine diphosphate, and presumably this is the reaction which supplies the energy for the contraction process. It would be of importance to establish this directly by demonstrating the breakdown of adenosine triphosphate during or before contraction. Such work is in progress, but it advances slowly on account of the experimental difficulties. A crude approximation to this experiment consists of immersing the tissue suddenly into liquid air: the intense cold acts as a stimulus and causes the tissue to be frozen in the contracted state. In this way, we find that about 0.5 /iM. of adenosine triphosphate per gram tissue undergoes chemical change in contraction, but the experiment is so crude