Excitation-Contraction Coupling and Cardiac Contractile Force

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 &endash; 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.

`Since the first edition of Excitation-Contraction Coupling and Cardiac Contractile Force was published 10 years ago, it has become a classic. The second edition is stunning. It retains the zest and compact form of the first edition, contains the wealth of information and analysis that has become the Bers' hallmark and is well written. It is easy and delightful to read.'
W. Jonathan Lederer (excerpted from the Introduction).
`This second edition of a now classical text is both extensively revised and up-to-date. The many illustrations, a large number of which are new to this edition, supplement a clearly written text that is filled with useful information. For those who seek a lucid, comprehensive and authoritative description of the interlocked systems that control the heart beat, I know of no other source that approaches Bers' Excitation-Contraction Coupling and Cardiac Contractile Force.'
Arnold M. Katz
`This book is a breath of fresh (and educated and thoughtful and well-organized) air Don Bers has produced a remarkably approachable and informative volume, clearly superior to others in this field. Active researchers should buy this book for themselves and their students.'
Laurence L. Brunton

Inhalt

1. Major cellular structures involved in E-C coupling.- Sarcolemma and transverse tubules.- Extracellular space.- Sarcoplasmic reticulum.- Mitochondria.- Myofilaments.- Connections to the extracellular matrix.- Other cellular constituents.- 2. Myofilaments: The end effector of E-C Coupling.- Myofilament proteins.- Mechanism by which Ca activates contraction.- Acto-myosin ATPase.- The length-tension relationship.- The Ca sensitivity of the myofilaments.- Force-pCa relation in intact cardiac muscle.- Factors which influence the force-[Ca] relationship.- Force velocity curves.- 3. Sources and sinks of activator calcium.- General Scheme of Ca cycle in cardiac myocyte.- Cellular volume conventions and Ca fluxes.- Ca buffering in the cytosol.- Ca requirements for activation of contraction.- Ca dynamics during a twitch.- Sources and sinks of Ca.- Ca removal during relaxation.- Ca influx vs SR Ca release in contractile activation.- Mitochondrial Ca transport.- 4. Cardiac action potentials and ion channels.- Action potential & heterogeneity.- Resting Em Nernst potential & propagation.- Basic structure & function of ion channels.- Channel gating.- Na channels.- Ca channels.- K channels.- Cl channels.- Stretch-activated channels.- Non-selective channels.- Na/Ca exchange.- Na/K-ATPase.- Currents during ventricular action potential.- Pacemakers (AP Phase 4).- Early and delayed afterdepolarizations.- Reentry of excitation.- 5. Ca influx via sarcolemmal Ca channels.- Ca channel types.- Molecular characterization of Ca channels.- Ca channel selectivity and permeation.- Numbers of Ca channels.- Ca channel gating.- Amount of Ca entry via Ca channels.- Modulation of ICa by agonists and antagonists.- ?-adrenergic modulation of cardiac Ca current.- Other modulators of Ca current.- 6. Na/Caexchange and the sarcolemmal Ca-pump.- The sarcolemmal Ca-pump.- Na/Ca exchange.- Competition among Na/Ca exchange, sarcolemmal Ca-pump and SR Ca-pump during relaxation and at rest.- 7. Sarcoplasmic reticulum Ca uptake, content and release.- SR Ca-pump.- SR Ca content: Assessment in intact cardiac muscle and myocytes.- SR Ca release channel or ryanodine receptor.- 8. Excitation-contraction coupling.- Voltage-dependent Ca release (VDCR) and skeletal muscle E-C coupling.- Ca-induced Ca-release (CICR).- Local control and CICR.- Other E-C coupling mechanisms in heart.- IP3-induced Ca release (IP3ICR).- Summary.- 9. Control of cardiac contraction by SR and sarcolemmal Ca fluxes.- Species, regional and developmental differences.- Biphasic contractions.- Rest decay and rest potentiation.- Force-frequency relationships.- 10. Cardiac inotropy and Ca mismanagement.- Cardiac inotropy.- Ca mismanagement and negative inotropy.- Sites for induction of cardiac inotropy.- Conclusion.- References.