Cholesterol Regulation of Ion Channels and Receptors

LEVITAN, IRENA; BARRANTES, F.J.

John Willey & Sons

Lugar: Hoboke, New Jersey; Año: 2012 p. 310

978-0470874325

Over the last decade there has been an explosion of studies focusing on the role of cholesterol in the regulation of ion channels and membrane receptors., many of which have shown that changes in the level of membrane cholesterol regulate a variety of ion channels and receptors belonging to almost all known families of these proteins. Furthermore, multiple types of ion channels and receptors have been shown to exhibit a tendency to partition into specific membrane domains that are cholesterol enriched. It becomes increasingly clear, therefore, that cholesterol is a major regulator of ion channel and receptor function.   Increased levels of cholesterol in blood represent a major risk factor for the development of atherosclerosis, heart attack and stroke, as a consequence of which cholesterol sensitivity of ion channels and receptors is expected to play a key role in the impairment of numerous physiological processes, including excitability of cardiomyocytes, vascular smooth muscle cells and neurons, as well as dysfunction of endothelial cells and impairment of immune function.  It is critical, therefore, to understand the mechanisms of cholesterol regulation of ion channels and receptors in order to facilitate the development of new therapeutic strategies to alleviate the impact of pathological cholesterol conditions. In this book we bring together the most up-to-date knowledge about the role of cholesterol in the regulation of ion channels and receptors and the pathological implications of its effects.   The idea for this book originated in the symposium ?Cholesterol as a regulator of channel and receptor function? that we organized two years ago for the Annual Meeting of the American Biophysical Society, held in Boston in 2009. The speakers at the symposium, presented a diversity of complementary points of view about the mechanisms underlying cholesterol action on ion channels and receptors. In this book, we extend the topics to a comprehensive critical overview of the field. We are very grateful to our publishing editor, Dr. Anita Lekwani, who first approached us with the idea of developing our symposium into a full book and who has been tremendously helpful at all stages of the project.   Among the major concepts discussed are: regulation of ion channels and receptors by the physical properties of lipid bilayers and the mismatch between the hydrophobic domains of the proteins and the hydrophobic interior of the membrane specific cholesterol protein interactions in the regulation of ion channels and receptors and regulation of these proteins by aggregation into multi-protein signaling platforms (?rafts?). Several of the chapters present the latest insights into the structural determinants of cholesterol sensitivity of ion channels and receptors and analyse putative cholesterol binding sites with special emphasis on the physiological role of this sensitivity in different cell types. The combined essays present a thorough analysis of current thinking and breakthrough discoveries relating to cholesterol regulation of ion channels and receptors, leaving the debate wide open to further advances in the field.