Cardiac Cellular Electrophysiology

424 Pages·2002·17.19 MB·English

by  Edward Carmeliet

CARDIAC CELLULAR
ELECTROPHYSIOLOGY
BASIC SCIENCE FOR THE CARDIOLOGIST
1. B. Swyngbedauw (ed.): Molecular Cardiology for the Cardiologist. Second
Edition. 1998 ISBN: 0-7923-8323-0
2. B. Levy, A. Tedgui (eds.): Biology of the Arterial Wall. 1999
ISBN 0-7923-8458-X
3. M.R. Sanders, J.B. Kostis (eds): Molecular Cardiology in Clinical
Practice. 1999. ISBN 0-7923-8602-7
4. B. Ostadal, F. Kolar (eds.): Cardiac Ischemia: From Injury to Protection. 1999
ISBN 0-7923-8642-6
5. H. Scbunkert, G.A.I. Riegger (eds.): Apoptosis in Cardiac Biology. 1999
ISBN 0-7923-8648-5
6. A. Malliani, (ed.): Principles of Cardiovascular Neural Regulation in Health
and Disease. 2000 ISBN 0-7923-7775-3
7. P. Benlian : Genetics of Dyslipidemia. 200 1
ISBN 0-7923-7362-6
8. D. Young: Role of Potassium in Preventive Cardiovascular Medicine. 2001
ISBN 0-7923-7376-6
9. E. Carmeliet, J. Vereecke : Cardiac Cellular Electrophysiology. 2002
ISBN 0-7923-7544-0
KLUWER ACADEMIC PUBLISHERS - DORDRECHT/BOSTON/LONDON
CARDIAC CELLULAR
ELECTROPHYSIOLOGY
by
Edward Carmeliet
and
Johan Vereecke
Department ofP hysiology
K. UL. University Leuven
Belgium
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging-in-Publication Data
ISBN 978-1-4613-5692-9 ISBN 978-1-4615-1715-3 (eBook)
DOI 10.1007/978-1-4615-1715-3
Copyright © 2002 by Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 2002
Softcover reprint ofthe hardcover Ist edition 2002
Ali rights reserved. No part ofthis publication may be reproduced, stored in a
retrieval system or transmitted in any form or by any means, mechanical, photocopying,
recording, or otherwise, without the prior written permis sion of the publisher, Springer
Science+Business Media, LLC.
Printed on acid-free pap er.
The Publisher offers discounts on this book for bulk purchases. For further
information, send email to[[email protected]}
Dedicated to
Prof. Silvio Weidmann
and in memory of
Prof. Edouard Coraboeuf
Contents
Acknowledgements
Preface
General description of electrical activity
Ionic basis of resting and action potential 7
Excitability, pacemaking and conduction 67
Ionic currents and action potentials in cardiac cells 95
Modulation of electrical activity 179
Electrophysiological basis of the electrocardiogram 229
Acute ischaemia 253
Arrhythmias 279
Remodeling 307
References 331
Abbreviations 407
Index 411
Acknowledgements
For copyright permission to reproduce figures we should like to thank
the following publishers or societies:
Acad Press: IV. 13, IV.l7, IV.29, IV.3I, IV.32, V.24, V.28, V.29.
Am Physiol Soc: 1.4, IV.5, IV.6, IV.9, IV.12, IV.20, IV.24, V.S, V.18, V.20,
V.26, V.30, V.32, VII.20, VII.22.
Am Soc Clin Invest: V.33.
Am Soc Pharmacol Exp Ther: IV.I4.
Brit Med J Pub Co: V.2.
Cambridge University Press, The Physiological Society: 11.16, IV.I, IV.3,
IV.4, IV.7, IV.9, IV.10, IV.lS, IV.I9, IV.23, IV.27, IV.28, IV.30, IV.38,
IV.39, V.3, V.IO, V.I2, VIII.lS.
Can Cardiovasc Soc: VII.6.
Ed. J.B. Bailliere: VIII.I7.
Elsevier: 1.3, VII.I2, VII.IS, VII.I7, IX.6, IXI6, IX.I7.
Futura Publ Co Inc: V.7, VII.14, IX. to, IX.I2.
Harwood Acad Publ: IV.l7, IV.37.
Kluwer Acad Publ: V.9, V.14.
Lippincott Williams & Wilkins:
Circ Res: 11.31, III.8, IV.9, IV.Il, IV.l6, IV.22, IV.2S, IV.33, V.IS, V.l6,
V.2I, V.2S, VI.7, VII.I, VII.5, VII.8, VII.9, VII.I3, VII. 15, VII.l6,
VII. 19, VIII.2, VIII.3, VIII.S, VIII.8, VIII.9, VIII 16, VIII.I8, VIII.20,
VIII.2I, IX.2, IX.3, IX.4, IX.8, IX.II, IX.13, IX.I4.
Circulation: VI.8, VI.9, VII.7, VII.lO, VIII.6, VIII.lO, VIII.lI, VIII.I2,
VIII. 19, lXI, IX.5, IX.7, IX.9, IX.I8.
J Cardiovasc Pharmacol: V.27,
Nat Acad Sci USA: IV.26.
Nature Publ Group, Nature 11.26: IV. I.
Nature Pub I Group, British Journal of Pharmacology: V.3I.
Raven Press: V.4.
Rockefeller University Press, The Journal of General Physiology: 11.16,
IV.4, IV.2I, V.6.
Sinauer Ass: 11.29, 11.30.
Springer Verlag:
Pfliigers Archiv: IV.12, IV.14, IV.26, IV.38, VIII. I.
Basic Res Cardiolol: V.5.
Preface
This book on "Cardiac Cellular Electrophysiology" appears in a series of
"Basic Science for the Cardiologist". However in addition for use by
clinicians needing a more thorough understanding of the electro
physiological basis of heart function, this book is also intended for a wider
public, undergraduate students and medical students interested in the basis of
the electrical activity of the heart, graduate students, research workers,
pharmacologists, teachers in physiology, pharmacology and other
biomedical sciences. Our goal in writing the book was twofold. Our first aim
was to give a primer on basic electrophysiology, the cardiac action potential
and the physiological basis of the electrocardiogram. For many non
electrophysiologists, original papers in cellular electrophysiology are often
difficult to read. We wanted to provide the necessary background and to
convince the readers that cellular electrophysiology is not so difficult to
grasp after all. It was our intention to make these parts accessible to a wide
audience. Our second aim, after having introduced the basic concepts, was to
continue with giving an overview of the properties of the most important
ionic currents in the heart, and to treat their modulation, in order to deal with
the mechanisms underlying cardiac ischaemia, arrhythmias and remodeling.
A huge literature exists about cardiac electrophysiology. With the
invention of the patch clamp technique by Neher and Sakmann in 1981, the
field exploded, and with the more recent application of molecular biology to
the study of ion channels, a large literature exists about the functioning of
channels at the molecular and single channel level. However throughout the
book our emphasis is on function rather than on channel biophysics,
molecular biology or structure -function relations. Therefore our emphasis is
much more on whole cell currents and their relation to cardiac electrical
activity than on single channel studies.
Chapter I contains a brief general description of the electrical activity in
the heart. It defines the different phases of the action potential and their
variation in different parts of the heart.
Chapter II provides the ionic mechanisms underlying resting and action
potential. After introducing some general principles of electric circuit theory
Preface
and applying these principles to the movement of ions across cell
membranes, in a second section it briefly describes the electrophysiological
techniques used to study electrical properties at the protein, the cellular, the
multicellular and the organ level, emphasising cellular electrophysiological
methods. In the third section a brief overview is first given of the major
types of membrane transport processes, distinguishing primary active,
secondary active and passive processes, and making the distinction between
channels and carriers. This is followed with the principles of description and
analysis of ion channel properties, discussing ion permeation, channel
gating, regulation and block, channel molecular structure and distribution.
The initiation and the propagation of the action potential is the subject of
Chapter III. This chapter describes the concept and mechanisms of
excitability and automaticity, and the basic mechanism underlying normal
and abnormal conduction. It starts with the concept of threshold and the
factors modulating excitability. Next it treats automaticity and the main
determinants of 'the initiation of the heart beat'. In the last section it gives an
introduction to one-dimensional cable theory and its application to
propagation of the action potential. It describes the concepts of electrotonic
potential, source - sink, short-circuit current and liminal length, conduction
velocity and safety factor. It then deals with the complications introduced by
the three-dimensional structure of the heart and provides some background
information on discontinuous propagation, anisotropy, unidirectional
propagation, to lay a basis for understanding reentrant arrhythmias.
Chapter IV first describes the properties of the most important ionic
currents contributing to the electrical activity of the heart. The emphasis is
on currents that have been identified in human cardiac cells, or that appear to
be generally present in mammalian hearts. As such this chapter is somewhat
encyclopaedic, and reading of the properties of some of the transport
mechanisms may eventually be postponed until needed to understand some
topic treated in later chapters, especially since not all transport processes
have (yet) been identified in human cardiac cells. In the last section of this
chapter the action potential morphology in different cardiac cells is
explained in terms of the different ion transport mechanisms, as described in
the previous sections.
Chapter V deals with the modulation of the electrical activity by rate, by
the autonomic nervous system, by humoral, autocrine and paracrine factors
and by the hormonal state. It also treats the effects of drugs, and discusses
the problems related to antiarrhythmic treatment and possible future
approaches.
Chapter VI handles the electrophysiological basis of the electro
cardiogram and the normal electrocardiographic waves. It also briefly deals
with abnormalities of ST segment, T wave and U wave. This chapter also
Preface
includes the dispersion of action potential duration and its influence on the
electrocardiogram.
Chapter VII successively treats acute ischaemia and reperfusion.
Following a description of the biochemical alterations upon acute
interruption of the coronary circulation, a detailed analysis is presented of
the changes in resting and action potential, excitability and conduction, and
the mechanisms involved. The second section treats the biochemical and
electrophysiological changes occurring upon reperfusion, distinguishing
between reversible and irreversible phases.
Chapter VIII deals with arrhythmias. In a first part an analysis is
presented of the basic mechanisms, including automatism, triggered activity
and reentry. Emphasis is given to recent developments, such as anisotropic
reentry and spiral wave activity. In a second part we provide a description of
the origin and type of arrhythmias occurring under specific conditions. We
discuss arrhythmias during acute ischaemia and reperfusion, and arrhythmias
at a later stage of the infarct when remodeling becomes important. We also
deal with atrial fibrillation, congenital and acquired long QT syndromes, the
Brugada syndrome, and arrhythmias accompanying hypertrophy and heart
failure.
The final chapter in the book, Chapter IX, provides an analysis of
electrical remodeling processes that develop during certain patho
physiological conditions such as hypertrophy and heart failure, atrial
fibrillation, and myocardial infarction. In contrast to short-term changes
described in Chapter V on Modulation, these processes include mid-term and
long-term alterations of the function and structure of ionic channels,
receptors and signaling pathways. Similar long-term physiological
adaptations occur during preconditioning and artificial pacing. It is
considered that a better knowledge of the mechanisms underlying
remodeling may offer new therapeutical approaches.
We want to express our sincere and warm thanks to Mrs Lies Vereecke
Peeters, the wife of one of the authors, for her skilful work in making the
numerous original figures and schemes and in adapting published figures
and, in this way, fulfilling the wishes and dreams of the authors.
We want to dedicate the book to Prof. Silvio Weidmann and to the late
Prof. Edouard Coraboeuf, founding fathers of cardiac cellular electro
physiology. In 1949, they were the first to register cardiac action potentials
with microelectrodes during their stay in Prof. Alan Hodgkin's laboratory.
Edward Carmeliet
Johan Vereecke