Molecular Control Mechanisms in Striated Muscle Contraction addresses the molecular mechanisms by which contraction of heart and skeletal muscles is regulated, as well as the modulation of these mechanisms by important (patho)physiological variables such as ionic composition of the myoplasm and phosphorylations of contractile and regulatory proteins. For the novice, this volume includes chapters that summarize current understanding of excitation-contraction coupling in striated muscles, as well as the compositions and structures myofibrillar thick and thin filaments. For the expert, this volume presents detailed pictures of current understanding of the mechanisms underlying the CA2+ regulation of contraction in heart and skeletal muscles and discusses important directions for future investigation.

Striated muscle is the most common muscle type in the vertebrate body. This book describes in molecular terms the components and intracellular events responsible for the contraction and relaxation of striated muscle. The topic is introduced with a discussion of motile systems occurring throughout the biological world and their relation to the highly specialised contractile system of muscle. Professor Perry then goes on to discuss the mechanochemical process and the regulatory roles of calcium, I filament proteins and phosphorylation. The book ends with an examination of the role of dystrophin and its implications in Duchenne muscular dystrophy, the most common form of muscle disease. Molecular Mechanisms in Striated Muscle will provide an important source of information and current theory for researchers and postgraduate students in muscle physiology, biochemistry and medicine.

There has been a lot of debate concerning the nature of the molecular mechanism that produces filament sliding and muscle shortening. This book presents the different kinds of structural and mechanical evidence in favour of the swinging of myosin heads on actin during the contractile cycle.

This volume presents the proceedings of a muscle symposium, which was supported by the grant from the Fujihara Foundation of Science to be held as the Fourth Fujihara Seminar on October 28 -November 1, 2002, at Hakone, Japan. The Fujihara Seminar covers all fields of natural science, while only one proposal is granted every year. It is therefore a great honor for me to be able to organize this meeting. Before this symposium, I have organized muscle symposia five times, and published the proceedings: " Cross-bridge Mechanism in Muscle Contraction (University of Tokyo Press, 1978), "Contractile Mechanisms in Muscle" (plenum, 1984); "Molecular Mechanisms of Muscle Contraction" (plenum, 1988); "Mechanism of MyofIlament Sliding in Muscle contraction" (plenum, 1993); "Mechanisms of Work Production and Work Absorption in Muscle" (plenum, 1998). As with these proceedings, this volume contains records of discussions made not only after each presentation but also during the periods of General Discussion, in order that general readers may properly evaluate each presentation and the up-to-date situation of this research field. It was my great pleasure to have Dr. Hugh Huxley, a principal discoverer of the sliding fIlament mechanism in muscle contraction, in this meeting. On my request, Dr. Huxley kindly gave a special lecture on his monumental discovery of myofIlament-lattice structure by X-ray diffraction of living skeletal muscle. I hope general readers to learn how a breakthrough in a specific research field can be achieved.

Understanding the molecular mechanism of muscle contraction started with the discovery that striated muscle is composed of interdigitating filaments which slide against each other. Sliding filaments and the working-stroke mechanism provide the framework for individual myosin motors to act in parallel, generating tension and loaded shortening with an efficient use of chemical energy. Our knowledge of this exquisitely structured molecular machine has exploded in the last four decades, thanks to a bewildering array of techniques for studying intact muscle, muscle fibres, myofibrils and single myosin molecules. After reviewing the mechanical and biochemical background, this monograph shows how old and new experimental discoveries can be modelled, interpreted and incorporated into a coherent mathematical theory of contractility at the molecular level. The theory is applied to steady-state and transient phenomena in muscle fibres, wing-beat oscillations in insect flight muscle, motility assays and single-molecule experiments with optical trapping. Such a synthesis addresses major issues, most notably whether a single myosin motor is driven by a working stroke or a ratchet mechanism, how the working stroke is coupled to phosphate release, and whether one cycle of attachment is driven by the hydrolysis of one molecule of ATP. Ways in which the theory can be extended are explored in appendices. A separate theory is required for the cooperative regulation of muscle by calcium via tropomyosin and troponin on actin filaments. The book reviews the evolution of models for actin-based regulation, culminating in a model motivated by cryo-EM studies where tropomyosin protomers are linked to form a continuous flexible chain. It also explores muscle behaviour as a function of calcium level, including emergent phenomena such as spontaneous oscillatory contractions and direct myosin regulation by its regulatory light chains. Contraction models can be extended to all levels of calcium-activation by embedding them in a cooperative theory of thin-filament regulation, and a method for achieving this grand synthesis is proposed. Dr. David Aitchison Smith is a theoretical physicist with thirty years of research experience in modelling muscle contractility, in collaboration with experimental groups in different laboratories.

It is now widely recognized that fundamental progress in science is made not in a continuous manner but in a stepwise manner. In the field of the molecular mechanism of contraction in striated muscle, the stepwise progress was achieved by three great investigators in 1940's and 1950's. In the early 1940's, Albert Szent-Gyorgyi and his associates showed biochemically that muscle contraction is essentially an interaction between actin and myosin coupled with ATP hydrolysis. Then, in the 1950's, Hugh E. Huxley together with Jean Hanson demonstrated that striated muscle is composed of a hexagonal lattice of two kinds of interdigtating myofilaments consisting of action and myosin respectively, and made a monumental discovery that muscle contraction results from the relative sliding between the actin and myosin filaments. Andrew F. Huxley, who also participated in the discovery of the sliding filament mechanism of muscle contraction was attributed to the attachment-detachment cycle between the cross-bridges extending from the myosin filament and the complementary sites on the actin filament. After the above stepwise progress, however, muscle research appears to have entered into a period of so-called 'normal science' where detailed knowledge has been accumulating around the well established 'central dogmas' but without fundamental progress. More specifically, most experiments on muscle contraction mechanisms have been designed, carried out and interpreted on the basis of the Huxley's 1957 and the Huxley-Simmons' 1971 contraction models, as well as the kinetic scheme of actomyosin ATPase; but the molecular mechanism of contraction still remains to be a matter for debate and speculation. For further fundamental progress in this field of research, we feel it necessary to reconsider the validity of these dogmas and to interpret the results more freely. In 1978, one of us (H.S.) organized a symposium in Tokyo based on the above idea, and we published the proceedings under the title of "Cross-bridge Mechanism in Muscle Contraction" (ed. H. Sugi and G.H. Pollack, University of Tokyo Press/University Park Press, 1979). The unusual interest of muscle physiologists in this symposium encouraged us to organize a second symposium on muscle contraction in Seattle in 1982, and proceedings was again published under the title of "Contractile Mechanisms in Muscle" (ed. G.H. Pollack and H. Sugi, Plenum Publishing Corporation, 1984). We were again very much encouraged by the intense interest of the people at the symposium as well as by readers of the proceedings, and became convinced that the symposia of this kind would greatly accelerate the progress in this field. The present symposium was organized by one of us (H.S.) as the third "Cross-bride" symposium. Though most papers are concerned, as in the previous two symposia, with experiments on intact and demembranated muscle fibers and isolated myofibrils, where the three-Dimensional muofilament-lattice structures have been preserved, the results are frequently discussed in connection with the kinetics of actomyosin ATPase, reflecting the recent development of experimental methods connecting physiology and biochemistry. It has also become possible to obtain direct information about the orientation and configuration of the cross-bridges as various stages during muscle contraction.