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Cholesterol Regulation of Ion Channels and Receptors

ISBN: 978-1-118-34230-5
300 pages
June 2012
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Examines new research on the role of cholesterol in regulating ion channels and receptors and its effect on health

Drawing together and analyzing all the latest research findings, this book explores the role of cholesterol in the regulation of ion channels and receptors, including its pathological effects. It is the first book to comprehensively describe the complex mechanisms by which cholesterol regulates two major classes of membrane proteins. Moreover, it sheds new light on how cholesterol affects essential cellular functions such as the contraction of the heart, propagation of nerve impulses, and regulation of blood pressure and kidney function.

Written and edited by leading pioneers in the field, Cholesterol Regulation of Ion Channels and Receptors is divided into three parts:

  • Part I, Cholesterol Regulation of Membrane Properties, introduces the heterogeneity of cholesterol distribution in biological membranes and the physical and biological implications of the formation of cholesterol-rich membrane domains.
  • Part II, Cholesterol Regulation of Ion Channels, examines the mechanisms underlying cholesterol sensitivities of ion channels, including the regulation of ion channels by cholesterol as a boundary lipid.
  • Part III, Cholesterol Regulation of Receptors, explores the latest discoveries concerning how cholesterol regulates distinct types of receptors, including G-protein coupled receptors, LDL and scavenger receptors, and innate immune system receptors.

Increased levels of cholesterol represent a major health risk. Understanding cholesterol regulation of ion channels and receptors is essential for facilitating the development of new therapeutic strategies to alleviate the impact of pathological cholesterol conditions. With this book as their guide, readers have access to the most current knowledge in the field.

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FOREWORD vii

PREFACE ix

CONTRIBUTORS xi

I CHOLESTEROL REGULATION OF MEMBRANE PROPERTIES 1

1 CHOLESTEROL TRAFFICKING AND DISTRIBUTION BETWEEN CELLULAR MEMBRANES 3
Daniel Wu¨ stner, Lukasz Michael Solanko, and Frederik W. Lund

2 CHOLESTEROL REGULATION OF MEMBRANE PROTEIN FUNCTION BY CHANGES IN BILAYER PHYSICAL PROPERTIES—AN ENERGETIC PERSPECTIVE 27
Jens A. Lundbæk and Olaf S. Andersen

II CHOLESTEROL REGULATION OF ION CHANNELS 45

3 INSIGHTS INTO STRUCTURAL DETERMINANTS OF CHOLESTEROL SENSITIVITY OF KIR CHANNELS 47
Avia Rosenhouse-Dantsker and Irena Levitan

4 ROLE OF LIPID RAFTS IN THE REGULATION OF STORE-OPERATED CA2+ CHANNELS 69
Hwei L. Ong and Indu S. Ambudkar

5 CHOLESTEROL REGULATION OF CARDIAC ION CHANNELS 91
Elise Balse, Ste´ phane Hatem, and Stanley Nattel

6 DIFFERENTIAL CONTRIBUTION OF BK SUBUNITS TO NONGENOMIC REGULATION OF CHANNEL FUNCTION BY STEROIDS 109
Alex M. Dopico, Anna N. Bukiya, and Aditya K. Singh

7 REGULATION OF K+ CHANNELS BY CHOLESTEROL-RICH MEMBRANE DOMAINS IN THE IMMUNE SYSTEM 135
Nu´ ria Comes and Antonio Felipe

8 INDIRECT CHANNEL REGULATION BY CHOLESTEROL: THE ROLE OF CAVEOLAE AND CAVEOLINS IN REGULATING KATP CHANNEL FUNCTION 161
Caroline Dart

III CHOLESTEROL REGULATION OF RECEPTORS 181

9 REGULATION OF THE NICOTINIC ACETYLCHOLINE RECEPTOR BY CHOLESTEROL AS A BOUNDARY LIPID 183
Francisco J. Barrantes

10 SPECIFIC AND NONSPECIFIC REGULATION OF GPCR FUNCTION BY CHOLESTEROL 205
Gerald Gimpl and Katja Gehrig-Burger

11 STRUCTURAL INSIGHTS INTO CHOLESTEROL INTERACTIONS WITH G-PROTEIN-COUPLED RECEPTORS 231
Jeremiah S. Joseph, Enrique E. Abola, and Vadim Cherezov

12 MEMBRANE CHOLESTEROL: IMPLICATIONS IN RECEPTOR FUNCTION 255
Sandeep Shrivastava and Amitabha Chattopadhyay

13 THE ROLE OF CHOLESTEROL AND LIPID RAFTS IN REGULATION OF TLR RECEPTORS 273
Ruxana T. Sadikot

INDEX 281

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IRENA LEVITAN, PhD, is Associate Professor of Medicine at the University of Illinois College of Medicine at Chicago. Her research interests focus on the impact of dyslipidemia on K+ channels and endothelial biomechanics.

FRANCISCO J. BARRANTES is the former head of the National Research Council (CONICET) – Bahia Blanca and UNESCO Chair of Biophysics and Molecular Neurobiology. Currently, he is Director of the Laboratory of Molecular Neurobiology and Professor at the Faculty of Medical Sciences, Pontifical Catholic University of Argentina. His current research interests focus on the understanding of nicotinic acetylcholine receptor-membrane cross-talk.

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