Download or read book Influence of the Thin Filament Calcium Activation on Muscle Force Production and Rate of Contraction in Cardiac Muscle written by Catalina Norman and published by . This book was released on 2007 with total page 197 pages. Available in PDF, EPUB and Kindle. Book excerpt: These results have physiological relevance and possible clinical applications considering that, on a beat-to-beat basis, the heart contracts at submaximum Ca2+ activation. In heart failure, Ca2+ sensitizing TnC mutants would increase the rate of contraction and improve contractility, whereas in hypertrophic cardiomyopathy, Ca2+ desensitizing TnC mutants would correct for the cardiac sensitization and/or the hypercontractile state.

Download or read book The Effects of Varying the Level of Thin Filament Activation in the Regulation of Muscle Contraction written by Carl A. Morris and published by . This book was released on 1999 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular and Cellular Aspects of Muscle Contraction written by Haruo Sugi and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 675 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Identifying Mechanisms of Thin Filament Activation in Cardiac Muscle Contraction written by John L. Williams and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: ABSTRACT: Myocardial contractions are generated by the binding of myosin motor proteins to cardiac actin in the thin filament. This process is regulated by the binding of calcium ions to troponin C. When Ca2+ binds to site II of troponin C, the troponin complex undergoes a conformational change which displaces tropomyosin and uncovers the myosin-binding sites on actin. This allows myosin to bind, and in the presence of ATP, allows for cross-bridges to cycle in order to generate force. While calcium binding to troponin is considered to be the key regulating mechanism for striated muscle contraction, myosin cross-bridges are also thought to play a role in cooperatively activating the thin filament. This cross-bridge contribution to thin filament activation appears to be more important in cardiac muscle systems than it is in skeletal muscle. However, many of these experiments examined the effects of cross-bridges under non-physiological conditions, leading to questions about the importance of actively cycling cross-bridges. Furthermore, there are questions as to the contribution of cross-bridge activation under conditions of low cross-bridge number, such as during filament sliding, primarily due to the inability to effectively change the number of cross-bridges that bind within a system in a controlled manner. In order to examine this possibility, I developed a porcine cardiac heavy meromyosin fragment that could be used to effectively vary the amount of myosin cross-bridges present in the in vitro motility assay. Additionally, I utilized this fragment at varying concentrations to determine several key characteristics of the cooperative mechanisms that govern thin filament activation. As a result, it was determined that cardiac myosin is sensitive to temperature when being proteolytically cleaved to form pcHMM, and subsequently, the protocol for making pcHMM requires decreasing the reaction temperature and increasing the protease concentration in order to yield a functional fragment. Secondly, it was determined that cardiac myosin cross-bridges number plays a minimal role in enhancing the activation of the thin filament by Ca2+ during unloaded filament sliding, and that this contribution in cardiac systems will be seen in the presence of a high density of actively cycling motors. Lastly, it is suggested that the enhancement that is seen due to increased numbers of cycling cardiac motors may be due to the regulatory proteins modulating the speed of myosin cycling, which is consistent with previously published literature. These findings help to advance our understanding of the contractile process and increase our understanding of the molecular complexities that govern thin filament activation by Ca2+.

Download or read book Muscle Biophysics written by Rassier Dilson J.E and published by Springer Science & Business Media. This book was released on 2010-09-08 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book New Concepts in the Control of Muscle Contraction written by Gerry A. Smith and published by Rowans Scientific. This book was released on 2007 with total page 102 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is a collection of papers that presents a novel interpretation of data from the literature to reason logically for an overlooked mechanism of stimulus-contraction coupling in muscle. This mechanism is then used to explain aspects of the puzzles relating to both an important physiological function of the heart, The Frank-Starling Law, and the basis of a common inherited disease state, familial hypertrophic cardiomyopathy (FHCM).

Download or read book Calcium in Muscle Activation written by Johann C. Rüegg and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a comparative and interdisciplinary approach to excitation-contraction-coupling in smooth and striated mus cles, including the myocardium. It is an account of the path ways and mechanisms by which cellular calcium is handled and activates the contractile proteins. It also describes how these mechanisms are adapted in various kinds of muscle to meet specific functional requirements, such as speed or economy. This monograph then presents facts, ideas and theories and the evidence on which they are based, and ifit stimulates others and furthers research, it will have served its purpose. All of the chapters are self-contained and may be read in any order, but readers unfamiliar with muscle are recommended to start with the introductory chapter on excitation and contraction. During all the years of writing this book, I received enormous help from Isolde Berger who corrected, edited and transformed my innumerable notes and drafts into a readable manuscript; she also compiled the list of references and the Subject Index. I owe a great debt of gratitude to her and also to Claudia Zeugner, who prepared the figures with expertise and care. Then I would like to thank the Deutsche F orschungs gemeinschaft and the Fritz-Thyssen-Stiftung for supporting the work of my Department which has been reported in this monograph. A great many people contributed with helpful discussions.

Download or read book Regulatory Mechanisms of Striated Muscle Contraction written by Setsuro Ebashi and published by Springer Science & Business Media. This book was released on 2007-05-14 with total page 398 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers the entire spectrum of research on troponin and related muscle proteins, including pathophysiological and clinical aspects. It details recent advances in work on the genetic disorders of cardiac troponin and ryanodine receptor proteins. Many color figures illustrate the three-dimensional structures of the proteins involved in the muscle functions. The book will help readers understand characteristic features of the regulatory mechanisms of striated muscle contraction and their disorders at the molecular level.

Download or read book Muscular Contraction written by Robert Malcolm Simmons and published by Cambridge University Press. This book was released on 1992-06-26 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: Composed of a set of chapters contributed by past and present collaborators of the Nobel laureate Sir Andrew Huxley, this book covers the areas of muscle research to which Huxley made major contributions. The purpose of the book is to discuss the way that muscles work, asking questions at a fundamental level about the molecular basis of muscle tone production and muscle contraction. The majority of the chapters are concerned with muscle physiology and the relation between structure and function. The process of activation of muscles is discussed, along with the mechanism of contraction itself. Although most of the book deals with vertebrate skeletal muscle, several chapters cover cardiac muscle. Also featured are two chapters discussing Sir Andrew's achievements in both nerve and muscle physiology.

Download or read book The Sliding Filament Theory of Muscle Contraction written by David Aitchison Smith and published by Springer. This book was released on 2019-02-05 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Exploring the Effect of Physiologically Relevant Protein Modifications on Cardiac Muscle Thin Filament Ca2 Binding and Engineering TnC to Correct Disease Related Aberrant Thin Filament Ca2 Binding written by Bin Liu and published by . This book was released on 2010 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The Ca2 sensitivity of cardiac muscle force development can be modulated by physiological or patho-physiological stimuli such as phosphorylation or disease related protein modification. Since troponin C (TnC) is the Ca2 sensor for cardiac muscle contraction, TnC's Ca2 binding properties could be affected by these physiological or patho-physiological related protein modifications. Thus, in this study, we examined the effect of mimicking phosphorylation and disease related protein modifications in TnI and TnT on the Ca2+ binding properties of TnC in a physiologically relevant biochemical model system, i.e. reconstituted thin filaments. Our results demonstrated that these protein modifications alter thin filament Ca2+ binding in a way generally consistent with their effect on myofilament Ca2+ sensitivity. Besides steady state Ca2+ binding affinity, the kinetic rate of Ca2+ dissociation from thin filament was also modulated by these physiologically relevant protein modifications. Generally, the protein modifications that sensitize thin filament Ca2+ binding usually slow the rate of Ca2+ dissociation from thin filament, while those that desensitize thin filament Ca2+ binding usually accelerate the rate of Ca2+ dissociation from thin filament. Experimental evidence suggests that the symptoms of some cardiac dysfunctions may be caused by the aberrant Ca2+ binding. Thus, correcting the aberrant Ca2+ binding might improve cardiac function. To achieve this goal, we have engineered TnC constructs with a wide, yet adjustable, range of Ca2+ binding sensitivities by modulating the negatively charged residues in the Ca2+ chelating loop and/or by replacing key hydrophobic amino acids in the regulatory domain of TnC with polar Gln. We were able to correct both the increased and decreased thin filament Ca2+ sensitivities caused by the disease associated proteins via replacing the wild type TnC with specifically engineered TnC constructs. Additionally, engineered TnC constructs can correct the disease related abnormal Ca2+ sensitivity of the thin filament acto-myosin ATPase assay and the force-pCa relationship in skinned trabeculae isolated from rat hearts. This study can potentially lead to a novel therapeutic strategy for treating cardiac muscle diseases.

Download or read book Calcium in Muscle Contraction written by Johann C. Rüegg and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent years have witnessed an explosion of knowledge lea- ding to a molecular understanding of the mechanisms of ac- tion of calcium on excitation and contraction coupling and its role in the regulation of contractility. This book highlights the most recent progress as well as providing a historial perspective of the field. It presents a concise and comprehensive overview of our current knowledge regar- ding calcium channels and regulatory proteins as well as in- tracellular calcium handling and the mechanisms underlying the activation of contractile proteins. It also describes how these basic mechanisms have been adapted in various types of muscle, especially in cardiac and smooth muscle.

Download or read book Molecular Control Mechanisms in Striated Muscle Contraction written by R.J. Solaro and published by Springer Science & Business Media. This book was released on 2013-04-17 with total page 469 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Excitation Contraction Coupling in Skeletal Cardiac and Smooth Muscle written by George B. Frank and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Third International Symposium on Excitation-Contraction Coupling in Skeletal, Cardiac, and Smooth Muscle, organized by George Frank, C. Paul Bianchi, and Henk E. DJ. ter Keurs, was held in Banff Centre, Banff, Alberta, Canada during June 26 to June 30, 1991. The theme of these symposia has been to recognize the similarities and dissimilarities of excitation-contraction coupling in skeletal, cardiac, and smooth muscle. Cross fertilization of concepts of excitation-contraction coupling in these three types of muscle has occurred since the early studies in the late fifties and early sixties on skeletal muscle. Investigators in each field meet only at specialized symposia which exclude investigators in the other fields. The purpose of the symposia has been to bring together international investigators studying excitation-contraction coupling in skeletal, cardiac, and smooth muscle so that we may learn from each other and hence provide a more global concept of excitation-contraction. The Third International Symposia has accomplished its objective as we recognize that calcium channels of the sarcolemma and the sarcoplasmic reticulum play key essential roles in excitation-contraction coupling in all three types of muscles. In skeletal muscle the recognition that E-C coupling consists of two parallel mechanisms, one dependent upon a dihydropyridine voltage-sensitive sensors coupled to calcium release from the terminal cisternae via the ryanodine sensitive channel in the foot structure of the triad.

Download or read book Effect of the Ca2 Binding Properties of Troponin C on Skeletal and Cardiac Muscle Force Development written by Ryan S. Lee and published by . This book was released on 2010 with total page 64 pages. Available in PDF, EPUB and Kindle. Book excerpt: Additionally, a protocol was developed to passively exchange whole human Tn into rat skinned cardiac trabeculae to study how TnC works in conjunction with other thin filament proteins to regulate the Ca2 sensitivity of force production. To this end, the disease related abnormal Ca2 sensitivities resulting from a truncation of TnI (residues 1-192) and a single residue K210 TnT deletion on the force-pCa relationship were first chracterized. TnCs were then specifically engineered and combined with these disease related mutations in hopes of correcting their effects on the Ca2 sensitivity of force. Our results demonstrate that TnC is able to attenuate and even completely restore dysfunctional Ca2+ sensitivity of force generation due to TnI or TnT modifications. Thus, it has been shown that TnC can control the rate of contraction by modulating the level of thin filament activation and is capable of correcting the aberrant Ca2+ binding properties due to modifications in other thin filament proteins.

Download or read book Regulation of Cardiac Contraction by Calcium and Crossbridges written by Karen L. Reece and published by . This book was released on 2007 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Excitation Contraction Coupling and Cardiac Contractile Force written by Donald Bers and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 468 pages. Available in PDF, EPUB and Kindle. Book excerpt: How is the heartbeat generated? What controls the strength of contraction of heart muscle? What are the links between cardiac structure and function? How does our understanding of skeletal and smooth muscle and non-muscle cells influence our thinking about force development in the heart? Are there important species differences in how contraction is regulated in the heart? How do the new molecular data fit together in understanding the heart beat? What goes wrong in ischemia, hypertrophy, and heart failure? This book paints a modern `portrait' of how the heart works and in this picture the author shows a close-up of the structural, biochemical, and physiological links between excitation and contraction. The author takes the reader through a series of important, interrelated topics with great clarity and continuity and also includes many useful illustrations and tables. The book starts by considering the cellular structures involved in excitation-contraction coupling and then described the characteristics of the myofilaments as the end effector of excitation-contraction coupling. A general scheme of calcium regulation is described and the possible sources and sinks of calcium are discussed in simple, but quantitative terms. The cardiac action potential and its many underlying currents are reviewed. Then the characteristics of some key calcium transport systems (calcium channels, sodium/calcium exchange and SR calcium uptake and release) are discussed in detail. This is then built into a more integrated picture of calcium regulation in succeeding chapters by detailed discussions of excitation-calcium coupling mechanisms (in skeletal, cardiac, and smooth muscle), the interplay between calcium regulatory processes, and finally mechanisms of cardiac inotropy, calcium overload, and dysfunction (e.g., ischemia, hypertrophy, and heart failure). Excitation-Contraction Coupling and Cardiac Contractile Force – Second Edition is an invaluable source of information for anyone who is interested in how the heart beat is controlled and especially suited for students of the cardiovascular system at all levels from medical/graduate students through senior investigators in related fields.