Derek J. Chadwick & Jamie A. Goode 
Signalling Pathways in Acute Oxygen Sensing [PDF ebook] 

Oxygen sensing is a key physiological function of many tissues, but
the identity of the sensor, the signalling pathways linking the
sensor to the effector, and the endpoint effector mechanisms are
all subjects of controversy. This book evaluates the various
mediators that have been proposed, including the mitochondria,
NAD(P)H oxidases, cytochrome p450 enzymes, and direct effects on
enzymes and ion channels. There has been a resurgence of interest
in the role of mitochondria, based partly on the ability of
mitochondrial inhibitors to mimic hypoxia, but there is little
consensus concerning mechanisms. Some favour the view that the
primary signalling event is a reduction in cell redox state and
reactive oxygen species (ROS) due to general inhibition of the
electron transport chain (ETC); others support a key role for
complex III of the ETC and an increase in ROS generation, while
others doubt either of these components is the key intermediary.
All these hypotheses are discussed in the book, together with
conceptual problems concerning the ability of mitochondria to
respond to physiological hypoxia.

The other area of controversy covered in the book is the identity
of the endpoint effector(s). Some authors favour K+ channel
inhibition, followed by depolarization and Ca2+ entry via L-type
channels, while others propose that release of Ca2+ from
intracellular stores, or capacitative Ca2+ entry and other
voltage-independent pathways may be more important. The book also
describes evidence for an endothelium-dependent Ca2+-sensitizing
pathway involving Rho and possibly other kinases.

While some of these differences can be attributed to variation
between tissues, many must be related to differences in
interpretation or methodology. In this book, experts in the field
of acute oxygen sensing working in different tissues address these
controversies and their possible origins, and discuss possible
approaches whereby these controversies might be resolved.

The book will be of great interest to all those working in fields
where oxygen sensing is important, particularly cancer and wound
healing, as well as researchers in drug discovery and
biotechnology.

قائمة المحتويات

Symposium on Signalling pathways in acute oxygen sensing, held
at the Novartis Foundation, London, 25-27 January
2005.

Editors: Derek J. Chadwick (Organizer) and Jamie
Goode.

This symposium is based on a proposal made by Jeremy
Ward.

Michael Duchen Chair’s introduction.

Gregg L. Semenza, Larissa A. Shimoda and Nanduri R.
Prabhakar Regulation of gene expression by Hypoxia-Inducible
Factor.

Discussion.

Ineke P. Stolze, David R. Mole and Peter J.
Ratcliffe Regulation of HIF: prolyl hydroxylases.

Discussion.

General discussion I.

Daniel Peet and Sarah Linke Regulation of HIF:
asparaginyl hydroxylation.

Discussion.

José López-Barneo, Patricia Ortega-Sáenz,
José I. Piruat and María
García-Fernández Oxygen-sensing by ion channels and
mitochondrial function in carotid body glomus cells.

Discussion.

Keith J. Buckler, Beatrice A. Williams, Rodrigo Varas
Orozco and Christopher N. Wyatt The role of TASK-like
potassium channels in oxygen sensing in the carotid body.

Discussion.

Nanduri R. Prabhakar, Ying-Jie Peng, Guoxiang Yuan and
Ganesh K. Kumar Reactive oxygen species facilitate oxygen
sensing.

Discussion.

C. A. Nurse, J. Buttigieg, R. Thompson, M. Zhang and
E. Cutz Oxygen sensing in neuroepithelial and adrenal
chromaffin cells.

Discussion.

C. Peers, P. Kang, J. P. Boyle, K. E. Porter, H. A. Pearson,
I. F. Smith and P. J. Kemp Hypoxic regulation of Ca2+
signalling in astrocytes and endothelial cells.

Discussion.

General discussion II.

Paul J. Kemp, Sandile E. J. Williams, Helen S. Mason,
Phillippa Wootton, David E. Iles, Daniela Riccardi and
Chris Peers Functional proteomics of BK potassium channels:
defining the acute oxygen sensor.

Discussion.

Stephen L. Archer, Evangelos D. Michelakis, Bernard
Thébaud, Sebastien Bonnet, Rohit Moudgil, Xi-Chen
Wu and E. Kenneth Weir A central role for O2-sensitive
K+ channels and mitochondria in the specialized O2-sensing
system.

Discussion.

Gregory B. Waypa and Paul T. Schumacker Role for
mitochondrial reactive oxygen species in hypoxic pulmonary
vasoconstriction.

Discussion.

Norbert Weissmann, Ralph T. Schermuly, Hossein A.
Ghofrani, Jörg Hänze, Parag Goyal, Friedrich
Grimminger and Werner Seeger Hypoxic pulmonary
vasoconstriction–triggered by an increase in reactive oxygen
species?.

Discussion.

General discussion III.

Alison M. Gurney and Shreena Joshi The role of
twin pore domain and other K+ channels in hypoxic pulmonary
vasoconstriction.

Discussion.

A. Mark Evans, D. Grahame Hardie, Antony Galione, Chris
Peers, Prem Kumar and Christopher N. Wyatt
AMP-activated protein kinase couples mitochondrial inhibition by
hypoxia to cell-specific calcium signalling mechanisms in
oxygen-sensing cells.

Discussion.

Silke Becker, Gregory A. Knock, Vladimir Snetkov, Jeremy P.
T. Ward and Philip I. Aaronson Role of capacitative Ca2+
entry but not Na+/Ca2+ exchange in hypoxic pulmonary
vasoconstriction in rat intrapulmonary arteries.

Discussion.

Final general discussion.

Index of contributors.

Subject index.

عن المؤلف

The Novartis Foundation is an international scientific and educational charity which promotes the study and general knowledge of science and in particular encourages international co-operation in scientific research.