Table Of ContentCardiac and Vascular Biology
Editor-in-chief: Markus Hecker
Viacheslav Nikolaev
Manuela Zaccolo Editors
Microdomains
in the
Cardiovascular
System
Cardiac and Vascular Biology
Editor-in-chief
Markus Hecker
Inst. of Physiology & Pathophysiology, Heidelberg University, Heidelberg,
Germany
Series Editor
Johannes Backs
Department of Cardiology, Heidelberg University, Heidelberg, Germany
Marc Freichel
Institute of Pharmacology, Heidelberg University, Heidelberg, Germany
Thomas Korff
Inst. of Physiology & Pathophysiology, Heidelberg University, Heidelberg,
Germany
Dierk Thomas
Department of Internal Medicine III, Heidelberg University Hospital, Heidelberg,
Germany
The book series gives an overview on all aspects of state-of-the-art research on the
cardiovascular system in health and disease. Basic research aspects of medically
relevant topics are covered and the latest advances and methods covering diverse
disciplines as epigenetics, genetics, mechanobiology, platelet research or stem cell
biology are featured. The book series is intended for researchers, experts and
graduates, both basic and clinically oriented, that look for a carefully selected
collection of high quality review articles on their respective field of expertise.
More information about this series at http://www.springer.com/series/13128
Viacheslav Nikolaev • Manuela Zaccolo
Editors
Microdomains in the
Cardiovascular System
Editors
Viacheslav Nikolaev Manuela Zaccolo
Institute of Experimental Cardiovascular Department of Physiology,
Research Anatomy and Genetics
University Medical Center University of Oxford
Hamburg-Eppendorf Oxford
Germany United Kingdom
ISSN 2509-7830 ISSN 2509-7849 (electronic)
Cardiac and Vascular Biology
ISBN 978-3-319-54578-3 ISBN 978-3-319-54579-0 (eBook)
DOI 10.1007/978-3-319-54579-0
Library of Congress Control Number: 2017952370
© Springer International Publishing AG 2017
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Preface
Cardiovascular disease is the leading cause of death in the western world with an
enormous global health care burden. Heart failure affects around 26 million indi-
viduals worldwide costing dozens of billion dollar in the USA or Europe every year.
Despite intensive medication, the 5-year survival for heart failure patients remains
at only ~50%, and projections indicate a 46% prevalence increase from 2012 to
2030. Available therapeutic strategies are based on general blockade of neuro-
hormonal mechanisms using β-blockers and inhibitors of the renin-angiotensin-
aldosterone system. In addition, inhibitors or natriuretic peptide degradation was
recently introduced into the medical practice, while designer natriuretic peptides are
in clinical trials. However, treatment remains symptomatic and results are unsatis-
factory for a significant number of patients: current drugs associate with serious side
effects and are ineffective for some patient groups. Present therapeutic strategies
largely ignore signalling processes occurring in cardiomyocytes at the subcellular
level.
Evidence accumulating over the past few decades clearly shows that cardiac dis-
ease is associated with dramatic alterations in functionally relevant subcellular
microdomains where the major second messengers cAMP, cGMP and calcium
come into action. To understand how such microdomains work and regulate cardiac
function and disease, several new technologies, including biosensors for live cell
imaging as well as sophisticated biochemical, electrophysiological and non-optical
imaging techniques, have been developed and widely applied to cardiac and vascu-
lar cells. The wealth of data obtained this way has transformed the theory of second
messenger compartmentation into a widely accepted paradigm. It is also becoming
apparent that microdomains might be the key to development of more specific car-
diovascular therapeutics which could potentially lead to a breakthrough in heart
failure therapy and long desired improvement of patients’ survival and care.
This volume covers recent findings in the research area of second messenger
microdomains with the focus on the cardiovascular system and disease, presented
by the renowned leaders in the field. The first part covers cyclic nucleotide micro-
domains and includes chapters on cAMP and cGMP microdomains. The second
part is dedicated to calcium microdomains.
v
vi Preface
We are grateful to all authors who provided outstanding chapters for this book.
The book illustrates the work done in the field over the last decades and gives a good
account of how this research has significantly advanced our understanding of the
role of second messenger microdomains in cardiovascular physiology and patho-
physiology. With this knowledge it is now our common interest and goal to carry
these exciting insights over translational paths to new therapeutic applications.
Hamburg, Germany Viacheslav Nikolaev
Oxford, UK Manuela Zaccolo
2017
Contents
Part I Cyclic Nucleotide Microdomains
1 Receptor-Cyclic Nucleotide Microdomains in the Heart . . . . . . . . . . . . 3
Nadja I. Bork and Viacheslav O. Nikolaev
2 Membrane Microdomains and cAMP Compartmentation
in Cardiac Myocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Shailesh R. Agarwal, Rennolds S. Ostrom, and Robert D. Harvey
3 Function to Failure: Compartmentalization
of Cardiomyocyte Signaling by A-Kinase- Anchoring Proteins . . . . . . 37
John M. Redden, Kimberly L. Dodge-Kafka, and Michael S. Kapiloff
4 P harmacological Approaches for Delineating Functions
of AKAP- Based Signalling Complexes and Finding
Therapeutic Targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Katharina Schrade and Enno Klussmann
5 C hatting Second Messengers: PIP3 and cAMP . . . . . . . . . . . . . . . . . . . 85
Alessandra Ghigo, Flora Pirozzi, Mingchuan Li, and Emilio Hirsch
6 C yclic Nucleotide Phosphodiesterases and Compartmentation
in Normal and Diseased Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Ibrahim Bedioune, Pierre Bobin, Jérôme Leroy,
Rodolphe Fischmeister, and Grégoire Vandecasteele
7 c AMP Compartmentalisation and Hypertrophy of the Heart:
‘Good’ Pools of cAMP and ‘Bad’ Pools of cAMP Coexist
in the Same Cardiac Myocyte . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Anna Zoccarato and Manuela Zaccolo
8 S ubcellular Targeting of PDE4 in Cardiac Myocytes
and Generation of Signaling Compartments . . . . . . . . . . . . . . . . . . . . 143
Marco Conti
9 Cardiac cAMP Microdomains and Their Modulation
Using Disruptor Peptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Lauren Wills, Bracy A. Fertig, and George S. Baillie
vii
viii Contents
10 Computational Modeling of Cyclic Nucleotide Signaling
Mechanisms in Cardiac Myocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Claire Y. Zhao
11 Signalling Microdomains: The Beta-3 Adrenergic
Receptor/NOS Signalosome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
J. Hammond and J.-L. Balligand
12 Compartmentation of Natriuretic Peptide Signalling in Cardiac
Myocytes: Effects on Cardiac Contractility and Hypertrophy . . . . . . 245
Lise Román Moltzau, Silja Meier, Kjetil Wessel Andressen,
and Finn Olav Levy
13 Cyclic GMP/Protein Kinase Localized Signaling
and Disease Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Brian Leei Lin, David A. Kass, and Dong I. Lee
Part II Calcium Microdomains
14 Distribution and Regulation of L-Type Ca2+ Channels
in Cardiomyocyte Microdomains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Alexey V. Glukhov, Anamika Bhargava, and Julia Gorelik
15 The Role of Local Ca2+ Release for Ca2+ Alternans
and SR-Ca2+ Leak . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Karin P. Hammer and Lars S. Maier
16 The Control of Sub-plasma Membrane Calcium Signalling
by the Plasma Membrane Calcium ATPase Pump PMCA4 . . . . . . . . 341
Nicholas Stafford, Ludwig Neyses, and Delvac Oceandy
17 Calcium Microdomains in Cardiac Cells . . . . . . . . . . . . . . . . . . . . . . . 361
A.M. Gómez, T.R.R. Mesquita, J.J. Mercadier, J.L. Álvarez,
and J.P. Benitah
Part I
Cyclic Nucleotide Microdomains
