The Endothelium


Book Description

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References




Store-Operated Calcium Channels


Book Description

Store-operated calcium channels are found in most animal cells and regulate many cellular functions including cell division, growth, differentiation, and cell death. This volume provides a concise and informative overview of the principles of store-operated calcium entry and the key developments in the field from researchers who have led these advances. The overall goal of the volume is to provide interested students and investigators with sufficient information to enable a broad understanding of the progress and current excitement in the field. The volume contains a wealth of information that even experienced investigators in the field will find useful. - The volume provides a comprehensive overview of the mechanisms and functions of store-operated calcium channels - Contributors are authoritative researchers who have produced important advances in the field - The volume is well-illustrated with cartoons and data to facilitate easy comprehension of the subject




Anatomy and Physiology


Book Description




Calcium in Muscle Activation


Book Description

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.




Calcium Entry Channels in Non-Excitable Cells


Book Description

Calcium Entry Channels in Non-Excitable Cells focuses on methods of investigating the structure and function of non-voltage gated calcium channels. Each chapter presents important discoveries in calcium entry pathways, specifically dealing with the molecular identification of store-operated calcium channels which were reviewed by earlier volumes in the Methods in Signal Transduction series. Crystallographic and pharmacological approaches to the study of calcium channels of epithelial cells are also discussed. Calcium ion is a messenger in most cell types. Whereas voltage gated calcium channels have been studied extensively, the non-voltage gated calcium entry channel genes have only been identified relatively recently. The book will fill this important niche.




Anatomy & Physiology


Book Description

A version of the OpenStax text




Fundamentals of Anaesthesia


Book Description

The second edition of Fundamentals of Anaesthesia builds upon the success of the first edition, and encapsulates the modern practice of anaesthesia in a single volume. Written and edited by a team of expert contributors, it provides a comprehensive but easily readable account of all of the information required by the FRCA Primary examination candidate and has been expanded to include more detail on all topics and to include new topics now covered in the examination. As with the previous edition, presentation of information is clear and concise, with the use of lists, tables, summary boxes and line illustrations where necessary to highlight important information and aid the understanding of complex topics. Great care has been taken to ensure an unrivalled consistency of style and presentation throughout.




The Sliding-Filament Theory of Muscle Contraction


Book Description

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.




Biochemistry of Smooth Muscle Contraction


Book Description

This valuable resource provides a systematic account of the biochemistry of smooth muscle contraction. As a comprehensive guide to this rapidly growing area of research, it covers the structure and characteristic properties of contractile and regulatory proteins, with special emphasis on their predicted function in the live muscle. Also included in this book are intermediate filament proteins, and desmin and vimentin, whose function in smooth muscle is unknown; and several enzymes involved in the phosphorylation-dephosphorylation of contractile and other proteins.




Skeletal Muscle Circulation


Book Description

The aim of this treatise is to summarize the current understanding of the mechanisms for blood flow control to skeletal muscle under resting conditions, how perfusion is elevated (exercise hyperemia) to meet the increased demand for oxygen and other substrates during exercise, mechanisms underlying the beneficial effects of regular physical activity on cardiovascular health, the regulation of transcapillary fluid filtration and protein flux across the microvascular exchange vessels, and the role of changes in the skeletal muscle circulation in pathologic states. Skeletal muscle is unique among organs in that its blood flow can change over a remarkably large range. Compared to blood flow at rest, muscle blood flow can increase by more than 20-fold on average during intense exercise, while perfusion of certain individual white muscles or portions of those muscles can increase by as much as 80-fold. This is compared to maximal increases of 4- to 6-fold in the coronary circulation during exercise. These increases in muscle perfusion are required to meet the enormous demands for oxygen and nutrients by the active muscles. Because of its large mass and the fact that skeletal muscles receive 25% of the cardiac output at rest, sympathetically mediated vasoconstriction in vessels supplying this tissue allows central hemodynamic variables (e.g., blood pressure) to be spared during stresses such as hypovolemic shock. Sympathetic vasoconstriction in skeletal muscle in such pathologic conditions also effectively shunts blood flow away from muscles to tissues that are more sensitive to reductions in their blood supply that might otherwise occur. Again, because of its large mass and percentage of cardiac output directed to skeletal muscle, alterations in blood vessel structure and function with chronic disease (e.g., hypertension) contribute significantly to the pathology of such disorders. Alterations in skeletal muscle vascular resistance and/or in the exchange properties of this vascular bed also modify transcapillary fluid filtration and solute movement across the microvascular barrier to influence muscle function and contribute to disease pathology. Finally, it is clear that exercise training induces an adaptive transformation to a protected phenotype in the vasculature supplying skeletal muscle and other tissues to promote overall cardiovascular health. Table of Contents: Introduction / Anatomy of Skeletal Muscle and Its Vascular Supply / Regulation of Vascular Tone in Skeletal Muscle / Exercise Hyperemia and Regulation of Tissue Oxygenation During Muscular Activity / Microvascular Fluid and Solute Exchange in Skeletal Muscle / Skeletal Muscle Circulation in Aging and Disease States: Protective Effects of Exercise / References