Cardiac Muscle

Contractility describes the relative ability of the heart to eject a stroke volume (SV) at a given prevailing afterload (arterial pressure) and preload (end-diastolic volume; EDV). Various measures of contractility are related to the fraction as the SV/EDV or the ejection fraction, and the dynamics of ejection as determined from maximum pressure rise in the ventricles or arteries or from aortic flow velocities determined by echocardiography. At the cellular level, the ultimate determinant of contractility is the relative tension generation and shortening capability of the molecular motors (myosin cross-bridges) of the sarcomeres as determined by the rates and extent of Ca activation, the turnover kinetics of the cross-bridges, and the relative Ca responsiveness of the sarcomeres. Engagement of the regulatory signaling cascades controlling contractility occurs with occupancy and signal transduction by receptors for neurohumors of the autonomic nervous system as well as growth and stress signaling pathways. Contractility is also determined by the prevailing conditions of pH, temperature, and redox state. Short-term control of contractility is fully expressed during exercise. In long-term responses to stresses on the heart, contractility is modified by cellular remodeling and altered signaling that may compensate for a time but which ultimately may fail, leading to disorders.

Research centering on blood flow in the heart continues to hold an important position, especially since a better understanding of the subject may help reduce the incidence of coronary arterial disease and heart attacks. This book summarizes recent advances in the field; it is the product of fruitful cooperation among international scientists who met in Japan in May, 1990 to discuss the regulation of coronary blood flow.

In the ever-expanding field of heart research the needs of established re searchers, students and general readers can vary considerably, making it difficult therefore to cater for all types of audience within a single volume. The aim of this book has been to provide a comprehensive and up-to-date review of the structure of the heart, including its cell biology. The ultrastructure of the working myocardium and all portions of the conduction system, together with their development, is covered in detail. Also included are chapters on the morphometry of cardiac muscle, the innervation of the heart, cardiac hyper trophy and regeneration, and the development of the coronary circulation. A detailed review of cardiac muscle in cell culture is also provided. It is to be hoped that readers, whatever their background, will find the information contained herein useful for their needs. This work was supported by a grant from the National Heart Foundation of Australia. The authors wish to gratefully acknowledge the following people for their invaluable assistance in preparation of the manuscript: Professor Yasuo Uehara, D'r. Takashi· Fujiwara, Dr. Peter Baluk, Dr. Seiji Matsuda and Bill Kaegi for providing unpublished micrographs; Fabian Bowers, Patricia Murphy and Janet Bennett for typing; and Lucy Popadynec, Nella Puglisi, Maggie Mackie, Mary Delafield and Liana Butera for assistance with references and figure preparation. THE AUTHORS Contents A. General Introduction 1 Morphology of Cardiac Muscle 8 B.

The period between 1950 and 1980 were the golden unique insights into how pathological processes affect years of transmission electron microscopy and produced cell organization. a plethora of new information on the structure of cells This information is vital to current work in which that was coupled to and followed by biochemical and the emphasis is on integrating approaches from functional studies. TEM was king and each micrograph proteomics, molecular biology, genetics, genomics, of a new object produced new information that led to molecular imaging and physiology and pathology to novel insights on cell and tissue organization and their understand cell functions and derangements in disease. functions. The quality of data represented by the images In this current era, there is a growing tendency to of cell and tissues had been perfected to a very high level substitut e modern light microscopic techniques for by the great microscopists of that era including Palade, electron microscopy, because it is less technically Porter, Fawcett, Sjostrand, Rhodin and many others. At demanding and is more readily available to researchers- present, the images that we see in leading journals for This atlas reminds us that the information obtained by the most part do not reach the same technical level and electron microscopy is invaluable and has no substitute.

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.

Biophysical Aspects of Cardiac Muscle is based on the proceedings of the first cardiac muscle symposium held May 1977, at the Pahlavi University in Shiraz, Iran. The compendium deals with topics on the gating processes in excitable membranes; ionic transport mechanisms in the generation of cardiac action potential plateau; structure and function of the sarcotubular system; excitation-contraction coupling in heart muscle; and mechanisms of drug action in cardiac muscle. The book will be of value to physicians, cardiologists, physiologists, and researchers in the field of medicine and anatomy.

Cardiac Muscle: The Regulation of Excitation and Contraction is a 12-chapter text that covers the research studies on characterizing the ionic and molecular mechanisms that regulate excitation and contraction of cardiac muscle. This book describes first the ionic currents underlying diastolic depolarization and pacing of the heart. The discussions then shift to the mechanisms of action of calcium-channel antagonists; the regulation of calcium influx by indigenous factors, such as voltage- or calcium-mediated inactivation; the identification of fixed negative charges on the surface of the sarcolemma; and the regulation of gating and permeability of ion channels by these charges. These topics are followed by examining the molecular and ionic mechanisms that underlie the electrophysiologic actions of adrenergic and cholinergic neurotransmitters and peptide hormones. This text further explores the theoretical and experimental studies of the sodium-calcium exchange process, its stoichiometry, and how the exchanger might contribute to current flow during or after the action potential. Other chapters consider the mechanism of twitch and tonic tension regulation by cardiac glycosides and intracellular sodium and how toxic concentrations induce cardiac arrhythmias. A chapter highlights the identification of sarcolemmal binding sites for calcium, the likelihood that such binding or the release of calcium from the sarcoplasmic reticulum plays a role in the regulation of contraction and the release of calcium from the sarcoplasmic reticulum. The remaining chapters deal with the structural similarities among calcium-binding proteins of the contractile apparatus and the calcium channel, and the regulation of contraction by calcium-binding proteins. Physiologists, pathophysiologists, clinicians, researchers, and students who are interested in heart’s function will find this book invaluable.