Actomyosin and Muscle Contraction

The successful introduction of o-nitrobenzyl caged ATP into physiological media instigated interest in expanding the applications of caged release to a wide variety of biochemical systems. The list includes the mechanism of release of P in skeletal muscle, the function of cAMP in the relaxation of distal muscle, the ATP-induced mechanism of actomyosin in muscle contraction, and the activation of antitumor antibiotics to highly reactive pyrrolic-type intermediates responsible for DNA crosslinking reactions. " ... 

However, release of ADP and P from myosin is much slower. Actin activates myosin ATPase activity by stimulating the release of P and then ADP. Product release is followed by the binding of a new ATP to the actomyosin complex, which causes actomyosin to dissociate into free actin and myosin. The cycle of ATP hydrolysis then repeats, as shown in Figure 17.23a. The crucial point of this model is that ATP hydrolysis and the association and dissociation of actin and myosin are coupled. It is this coupling that enables ATP hydrolysis to power muscle contraction. 

That actin and myosin are jointly responsible for contraction was demonstrated long before the fine structure of the myofibril became known. In about 1929, ATP was recognized as the energy source for muscle contraction, but it was not until 10 years later that Engelhardt and Ljubimowa showed that isolated myosin preparations catalyzed the hydrolysis of ATP.138 Szent-Gyorgi139 140 showed that a combination of the two proteins actin (discovered by F. Straub141) and myosin was required for Mg2+-stimulated ATP hydrolysis (ATPase activity). He called this combination actomyosin. 

A family of actin-binding proteins that exist in various isoforms. As with other protein isoforms or isoenzymes, the expression of the isoforms is tissue-specific. The interaction of calponin with actin inhibits the actomyosin Mg-ATRase activity. See Winder, S. and Walsh, M., Inhibition of the actinomyosin MgATRase by chicken gizzard calponin. Prog. Clin. Biol. Res. 327, 141-148, 1990 Winder, S.J., Sutherland, C., and Walsh, M.R., Biochemical and functional characterization of smooth muscle calponin, Adv. Exp. Med. Biol. 304, 37-51, 1991 Winder, S.J. and Walsh, M.R., Calponin thin filament-linked regulation of smooth muscle contraction. Cell Signal. 5,677-686,1993 el-Mezgueldi, M., Calponin, Int. J. Biochem. 

Study of the molecular biology of calcium regulation of muscle contraction was initiated by the discovery of a new protein factor sensitizing actomyosin to calcium ions (Ebashi, 1963 Ebashi and Ebashi, 1964). This protein factor was called native tropomyosin, because of its similarity in amino acid composition to tropomyosin, which had been discovered earlier (Bailey, 1946, 1948). It was soon found that this factor is a complex of tropomyosin and a new globular protein, termed troponin (Ebashi and Kodama, 1965 Ebashi et al., 1968). Thus four proteins, i.e., myosin, actin, troponin, and tropomyosin, are involved in calcium-regulated physiological muscle contraction (Ebashi et al., 1968, 1969 Ebashi and Endo, 1968). The contractile interaction between myosin and actin is depressed by troponin and tropomyosin in the absence of calcium ions. When calcium ion acts on troponin, this depression is removed and the contractile interaction is then activated (Figs. 1 and 2). 

Both proteins bind to actin and calmodulin and have the capacity, in vitro at least, to inhibit the Mg-ATPase of smooth muscle actomyosin in a caldum-reg-ulated manner. This suggests that in smooth muscle also there is a mechanism for the regulation of modulation of contractile activity involving the thin filaments. It is clear that despite the enormous advances in knowledge there is much to be learned about the mechanism of regulation, and areas of controversy still exist. For this reason alone, a treatise such as Biochemistry of Smooth Muscle Contraction with detailed contributions by international experts is a very timely and important contribution to the literature. 

Matsunaga, K., Nakatani, K., Ishibashi, M., Kobayashi, J., and Ohizumi, Y. (1999). Amphidinolide B, a powerful activator of actomyosin ATPase enhances skeletal muscle contraction. Biochim. Biophys. Acta 1427, 24-32. 

Cross RA, Jackson AP, Citi S, Kendrick-Jones J, Bagshaw CR (1988) Active site trapping of nucleotide by smooth and non-muscle myosins. J Mol Biol 203 173-181 Dabrowska R (1994) In Raeburn D, Giembycz MA (eds) Airways smooth muscle biochemical control of contraction and relaxation. Birkhauser, Basle, pp 32-59 Dabrowska R, Goch A, Galazkiewicz B, Osinska H (1985) The influence of caldesmon on ATPase activity of the skeletal muscle actomyosin and bundling of actin filaments. Biochim Biophys Acta 842 70-75... 

Winder SJ, Walsh MP (1990) Smooth muscle calponin. Inhibition of actomyosin MgATPase and regulation by phosphorylation. J Biol Chem 265 10148-10155 Winder SJ, Walsh MP (1993) Calponin thin filament-linked regulation of smooth muscle contraction. Cell Signal 5 677-686 Winder SJ, Walsh MP (1996) Calponin. Curr Top Cell Regul 1996 34 33-61 Wingard CJ, Paul RJ, Murphy RA (1994) Dependence of ATP consumption on crossbridge phosphorylation in swine carotid smooth muscle. J Physiol (Lond) 481 111-117... 

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