Mechanism Of Muscular Contraction

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.

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.

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.

Editions previous to this one had R.D. Keynes and David J. Aidley as primary and secondary authors.

The extremely potent substance botulinum neurotoxin (BoNT) has attracted much interest in diverse fields. Originally identified as cause for the rare but deadly disease botulism, military and terrorist intended to misuse this sophisticated molecule as biological weapon. This caused its classification as select agent category A by the Centers for Diseases Control and Prevention and the listing in the Biological and Toxin Weapons Convention. Later, the civilian use of BoNT as long acting peripheral muscle relaxant has turned this molecule into an indispensable pharmaceutical world wide with annual revenues >$1.5 billion. Also basic scientists value the botulinum neurotoxin as molecular tool for dissecting mechanisms of exocytosis. This book will cover the most recent molecular details of botulinum neurotoxin, its mechanism of action as well as its detection and application.

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.

A version of the OpenStax text

Essential textbook for all undergraduate students of neurobiology, physiology, cell biology and preclinical medicine.

Muscle contraction has been the focus of scientific investigation for more than two centuries, and major discoveries have changed the field over the years. Early in the twentieth century, Fenn (1924, 1923) showed that the total energy liberated during a contraction (heat + work) was increased when the muscle was allowed to shorten and perform work. The result implied that chemical reactions during contractions were load-dependent. The observation underlying the “Fenn effect” was taken to a greater extent when Hill (1938) published a pivotal study showing in details the relation between heat production and the amount of muscle shortening, providing investigators with the force-velocity relation for skeletal muscles. Subsequently, two papers paved the way for the current paradigm in the field of muscle contraction. Huxley and Niedergerke (1954), and Huxley and Hanson (1954) showed that the width of the A-bands did not change during muscle stretch or activation. Contraction, previously believed to be caused by shortening of muscle filaments, was associated with sliding of the thick and thin filaments. These studies were followed by the classic paper by Huxley (1957), in which he conceptualized for the first time the cross-bridge theory; filament sliding was driven by the cyclical interactions of myosin heads (cross-bridges) with actin. The original cross-bridge theory has been revised over the years but the basic features have remained mostly intact. It now influences studies performed with molecular motors responsible for tasks as diverse as muscle contraction, cell division and vesicle transport.