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.