Cardiovascular Gap Junctions

307 Pages·2006·3.45 MB·English

by  S. Dhein

Cardiovascular Gap Junctions
Advances in Cardiology
Vol.42
Series Editor
Jeffrey S. Borer New York, N.Y.
Cardiovascular Gap
Junctions
Volume Editor
Stefan Dhein Leipzig
71 figures, 28 in color, and 4 tables, 2006
Basel·Freiburg·Paris·London·New York·
Bangalore·Bangkok·Singapore·Tokyo·Sydney
Advances in Cardiology
Prof.Dr.med.Stefan Dhein
Klinik für Herzchirurgie
Herzzentrum Leipzig
Universität Leipzig
Struempellstr. 39
D-04289 Leipzig (Germany)
Library of Congress Cataloging-in-Publication Data
Cardiovascular gap junctions / volume editor, Stefan Dhein.
p. ; cm. – (Advances in cardiology, ISSN 0065-2326 ; v. 42)
Includes bibliographical references and indexes.
ISBN 3-8055-8077-0 (hard cover : alk. paper)
1. Heart conduction system. 2. Gap junctions (Cell biology) 3. Arrhythmia. I. Dhein, S.
(Stefan) II. Dhein, S. (Stefan). Cardiovascular gap junctions. III. Series.
[DNLM: 1. Gap Junctions–physiology. 2. Heart Conduction System–physiology. 3. Gap
Junctions–drug effects. 4. Heart Diseases–physiopathology. W1 AD53C v.42 2006 /
WG 202 C2655 2006]
RC681.A25A38 vol. 42
[QP114.C65]
616.1(cid:1)2 s–dc22
[612.1(cid:1)7]
2006001441
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents®and
Index Medicus.
Disclaimer. The statements, options and data contained in this publication are solely those of the individ-
ual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the
book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness,
quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property
resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and
dosage set forth in this text are in accord with current recommendations and practice at the time of publication.
However, in view of ongoing research, changes in government regulations, and the constant flow of information
relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for
any change in indications and dosage and for added warnings and precautions. This is particularly important when
the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or
utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying,
or by any information storage and retrieval system, without permission in writing from the publisher.
© Copyright 2006 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel
ISSN 0065–2326
ISBN 3–8055–8077–0
Contents
VII Preface
1 Cardiac Connexins:Genes to Nexus
Duffy, H.S. (Bronx/New York, N.Y.); Fort, A.G.;
Spray, D.C. (Bronx, N.Y.)
18 Physiology of Cardiovascular Gap Junctions
van Veen, T.A.B.; van Rijen, H.V.M.; Jongsma, H.J. (Utrecht)
41 Role of Connexin43-Interacting Proteins at Gap Junctions
Giepmans, B.N.G. (La Jolla, Calif.)
57 Life Cycle of Connexins:Regulation of Connexin Synthesis and
Degradation
Salameh, A. (Leipzig)
71 Gap Junctions and Propagation of the Cardiac Action Potential
Bernstein, S.A.; Morley, G.E. (New York, N.Y.)
86 Micropatterns of Propagation
Lee, P.J.; Pogwizd, S.M. (Chicago, Ill.)
107 Pharmacology of Cardiovascular Gap Junctions
Hervé, J.-C. (Poitiers); Dhein, S. (Leipzig)
132 Structural and Functional Coupling of Cardiac Myocytes
and Fibroblasts
Camelliti, P. (Oxford); Green, C.R. (Auckland); Kohl, P. (Oxford)
V
150 Connexins and Cardiac Arrhythmias
van Rijen, H.V.M.; van Veen, T.A.B. (Utrecht); Gros, D. (Marseille);
Wilders, R. (Amsterdam); de Bakker, J.M.T. (Utrecht/Amsterdam)
161 Role of Connexins in Atrial Fibrillation
Dhein, S. (Leipzig)
175 Connexins in the Sinoatrial and Atrioventricular Nodes
Boyett, M.R.; Inada, S.; Yoo, S.; Li, J. (Manchester); Liu, J. (Oxford);
Tellez, J. (Manchester); Greener, I.D. (Leeds); Honjo, H. (Nagoya);
Billeter, R. (Leeds); Lei, M. (Oxford); Zhang, H. (Manchester);
Efimov, I.R. (St. Louis, Mo.); Dobrzynski, H. (Manchester)
198 Cardiac Ischemia and Uncoupling:Gap Junctions in Ischemia and
Infarction
Dhein, S. (Leipzig)
213 Connexin43 and Ischemic Preconditioning
Schulz, R.; Heusch, G. (Essen)
228 Alterations in Cardiac Connexin Expression in Cardiomyopathies
Severs, N.J.; Dupont, E.; Thomas, N.; Kaba, R.; Rothery, S.; Jain, R.;
Sharpey, K.; Fry, C.H. (London)
243 Alterations of Connexin 43 in the Diabetic Rat Heart
Lin, H.; Ogawa, K.; Imanaga, I. (Fukuoka); Tribulova, N. (Bratislava)
255 Connexins in Atherosclerosis
Chadjichristos, C.E.; Derouette, J.-P.; Kwak, B.R. (Geneva)
268 Connexin-Dependent Communication within the Vascular Wall:
Contribution to the Control of Arteriolar Diameter
de Wit, C.; Wölfle, S.E.; Höpfl, B. (Lübeck)
284 Cx40 Polymorphism in Human Atrial Fibrillation
Hauer, R.N.W.; Groenewegen, W.A.; Firouzi, M.; Ramanna, H.;
Jongsma, H.J. (Utrecht)
292 Author Index
293 Subject Index
Contents VI
Preface
. . . all the things do depend upon the motional pulsation of the heart:
Tothe heart is the beginning of life.
William Harvey,1653
With this sentence and his investigations, William Harvey started modern
cardiovascular research and medicine. While he was fascinated by mechanical
motion and discovered a basic principle of the cardiovascular system, recent
research focuses on motion itself and its regulation. The expression ‘motional
pulsation’somehow includes rhythm. The basis for this rhythmical motion is an
electrical activation wave leading to contraction, which has to propagate from
its origin at the sinus node to the whole heart. Thus ‘motional pulsation’encom-
passes another form of motion, a propagating electrical wave. This is made
possible by a network of communicating cells interconnected by gap junction
channels. However, these channels not only allow the transfer of electrical
signals, they also enable the transfer of small molecules which may serve as
signals for cell growth, death or differentiation. In addition, it has become clear
that these gap junction channels also importantly contribute to vascular motion.
It was the classic paper by N.B. Gilula (1944–2000), published in Nature
[Gilula et al., Nature, 1972;235:262–265], that provided the first clear evidence
that gap junctions are involved in exchange of metabolites and ions between
neighboring cells. Thereafter, our knowledge about these channels and their
functions has been enlarged by many elegant studies, and gap junction research
has become a focus in cell biology, since intercellular gap junction communica-
tion provides the basis of the organization of many organs as a cellular network.
VII
With these studies, it became increasingly evident that gap junctions signifi-
cantly contribute to the regulation of the cardiovascular system and that failure
or alterations of these channels lead to dysfunction.
Since the publication of Cardiac Gap Junctionsin 1998 [Dhein S, Cardiac
Gap Junctions. Physiology, Regulation, Pathophysiology and Pharmacology.
Basel, Karger] gap junction research in the cardiovascular system has consider-
ably grown and has largely improved our understanding of the regulation of the
heart and vasculature in health and disease. Several well-known gap junction
researchers in the cardiovascular field have contributed to the present edition of
this book, which is intended to give insight into this fascinating field. I wish to
thank them all for their help and support, as well as all the other gap junction
researchers who made these and my own studies possible with their basic find-
ings and seminal papers.
The first part of this book is focused on the major aspects of these intercel-
lular channels, allowing the readers who are not familiar with the field to get a
deeper understanding of gap junction physiology, pharmacology and regulation,
while the second part elucidates their role in the pathophysiology of a number
of important cardiovascular diseases, such as arrhythmia, heart failure, ischemia,
atrial fibrillation, diabetes and arteriosclerosis. Hopefully, this book will help
stimulate researchers to extend their investigations in this fascinating field, and
exchange their views and findings in an open communicating scientific net-
work, as the cells they are investigating do.
Stefan Dhein
Leipzig, October 2005
Preface VIII
Dhein S (ed): Cardiovascular Gap Junctions.
Adv Cardiol. Basel, Karger, 2006, vol 42, pp 1–17
Cardiac Connexins:Genes to Nexus
Heather S. Duffya,b, Alfredo G. Forta, David C. Spraya
aDepartment of Neuroscience, Albert Einstein College of Medicine, Bronx, N.Y.;
bDepartment of Pharmacology, Columbia University College of Physicians and
Surgeons, New York, N.Y., USA
Abstract
Gap junctions are formed of at least 20 connexin proteins in mammals and possibly
pannexins as well. Of the connexins, at least 5 (Cx30.2, Cx37, Cx40, Cx43 and Cx45) are
prominently expressed in the heart and each shows regional and cell type specific expres-
sion. Contributions of each of these connexins to heart function has been in many cases illu-
minated by connexin null mice. The cardiac connexin genes whose genomic organization
and transcriptional controls have been studied most thoroughly indicate more complex possi-
bilities for alternate promoter usage than originally thought as well a multiple transcription
factor binding sites; presumably, such complexity governs developmental timing and
regional connexin expression patterns. The structure of cardiac connexin proteins indicate
four primarily (cid:1)-helical transmembrane domains, cytoplasmic amino and carboxyl termini
and a cytoplasmic loop, all of which contain some regions of (cid:1)-helix, and extracellular loops
that are primarily (cid:2)-structure. A number of proteins that bind to cardiac connexins are
known, and more are certain to be discovered, linking the connexin into an intercellular sig-
naling complex, the nexus. Binding sites may either correspond to structured regions within
the connexin molecules or be unstructured, leading to presumably low-affinity and dynamic
interactions.
Copyright © 2006 S. Karger AG, Basel
Gap junctions in adult heart are found at the intercalated disk, localized
between the desmosomes and adherens junctions and in small amounts along
the lateral myocyte membranes. They are thought to function primarily in pas-
sage of electrical impulses from myocyte to myocyte, aiding the synchronous
electrical activity of the myocardium. As with desmosomes and adherens junc-
tions, mammalian gap junctions are randomly localized around the myocytes at
birth but unlike the other junctional types they remain more scattered during