Function of Creatine Kinase Localization in Muscle Contraction

Abstract

The creatine phosphate shuttle hypothesis, a central theme of the Congress, suggests that mitochondrial creatine kinase (CK) produces phosphocreatine (PCr) from ATP, that CK on or near the sarcomere produces ATP from PCr, and that energy is shuttled from mitochondria to the myofibrils via PCr. According to the hypothesis the CK reaction is crucial to the control of respiration and to the control of the microenvironment of the contractile apparatus. The nucleotide concentrations in the region of the myosin ATPase are thought to depend on the localization of CK on the sarcomere (Bessman and Geiger, 1981). Many studies have addressed the issue of CK localization on the mitochondrial membrane, and of the effects of nucleotide and PCr on oxidative respiration (Jacobus and Lehninger, 1973; Saks et al., 1980). At the opposite end of the shuttle, the sarcomere, there is evidence for CK localization on the M-line structure (Turner et al., 1973). This result motivated several investigations of CK interactions with myosin and with other M-line proteins. Although some studies came to the intriguing conclusion that CK binds to the head region of myosin, others failed to confirm this observation (Houk and Putnam, 1973; Botts et al., 1975; Mani et al., 1980; Woodhead and Lowey, 1983). The possibility of a direct interaction of CK with the myosin head suggests that the contractile mechanism may depend upon CK binding, and thus upon the CK concentration. However, the functional significance of the binding of CK to either myosin or the M-line has not been previously explored by physiological measurements of fiber contraction.