Molecular And Physiological Mechanisms Of Muscle Contraction

Thoroughly researched using experimentation and re-examination of all previously published evidence, Molecular and Physiological Mechanisms of Muscle Contraction is a carefully crafted treatise and revision of previous conceptions of muscle contraction. It presents detailed descriptions of new, previously unpublished data and hybrids recent findings with the standard Huxley model. This book demonstrates that traditional concepts cannot fully explain contraction and builds upon previous work. It identifies flaws in the reasoning initially used to explain some results as well as alternative interpretations accounting for inconsistencies. In response to previous bodies of inconsistent or conflicting theories and data, the book synthesizes research based on the Huxley model with more recent experimental and laboratory findings to define a new model. The new model this book proposes is not a replacement for the standard Huxley model of muscle contraction, but a modification based on recent research and synthesized with pre-existing data and conceptions. It reconciles new data with prior information that is contradictory or not entirely explicable in proposing a new integrated and more complete model of muscle contraction.

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.

This book describes the evolution of ideas relating to the mechanism of muscular contraction since the discovery of sliding filaments in 1954. An amazing variety of experimental techniques have been employed to investigate the mechanism of muscular contraction and relaxation. Some background of these various techniques is presented in order to gain a fuller appreciation of their strengths and weaknesses. Controversies in the muscle field are discussed along with some missed opportunities and false trails. The pathway to ATP and the high energy phosphate bond will be discussed, as well as the discovery of myosin, contraction coupling and the emergence of cell and molecular biology in the muscle field. Numerous figures from original papers are also included for readers to see the data that led to important conclusions. This book is published on behalf of the American Physiological Society by Springer. Access to APS books published with Springer is free to APS members.

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.

This volume intends to provide a comprehensive overview on the mecha nisms of muscle contraction and non-muscle cell motility at the molecu lar and cellular level, not only for investigators in these fields but also for general readers interested in these topics. A most attractive feature of various living organisms in the animal and plant kingdoms is their ability to move. In spite of a great diversity in the structure and function of various motile systems, it has frequently been assumed since the nineteenth century that all kinds of "motility" are essentially the same. Based on this assumption, some investigators in the nineteenth century thought that the mechanisms of motility could better be studied on primitive non-muscle motile systems such as amoeboid movement, rath er than on highly specialized muscle cells. Contrary to their expectation, however, the basic mechanisms of motility have been revealed solely by investigations on vertebrate skeletal muscles, since a monumental discovery of Szent-Gyorgyi and his coworkers in the early 1940s that muscle contraction results from the interaction between two different contractile proteins, actin and myosin, coupled with ATP hydrolysis.

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.

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.

Despite extensive physiological, biochemical, and structural studies, the mechanisms of muscle contraction operating in living muscle fibres are still not clearly understood. This book aims to describe and assess various experimental methods currently used in the field of muscle research. For each method discussed, there is a comprehensive description of its advantages, problems, and limitations. Each chapter also contains a summary of the central results to have been obtained using each method. Comprehensively written by experts in their respective fields, this book will be of interest to all investigators in muscle physiology.