Cholesterol Regulation of Ion Channels and Receptors

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John Wiley & Sons, Jun 12, 2012 - Science - 300 pages
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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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Contents

Bilayers and Cells
11 Cholesterolan Essential Lipid for Normal Cell Function
12 Cholesterol Metabolism Sensing and Distribution Between Cellular Membranes
13 How Does Cholesterol Enter Mammalian Cells?
14 Vesicular Cholesterol Trafficking Along the Endocytic and Secretory Pathway
15 Nonvesicular Cholesterol Transport
16 Cholesterol Efflux from Cells
21 Introduction
83 Concluding Remarks and Future Directions
2040
91 Introduction
2047
92 The AChR is Surrounded by Lipids in the LiquidOrdered Phase
2049
93 Stoichiometry and Selectivity of the ProteinVicinal Lipid
2050
94 Influence of Cholesterol on AChR Secondary Structure
2051
95 Influence of Cholesterol on AgonistInduced Conformational States and Ion Translocation Function
2052
from Bacterial Homologs to Eukaryotes
2053
97 Cholesterol Binding to Nonannular Sites on the AChR Molecule
2055

23 Protein Regulation by CholesterolInduced Changes in Bilayer Physical Properties
24 CholesterolInduced Changes in Quantitative Estimates
25 Methods for Identifying Protein Regulation by Changes in Bilayer Physical Properties
ii
26 Cholesterol Regulation of Membrane Proteins in Living Cells
iv
27 Physiological Role of CholesterolInduced Changes in Bilayer Physical Properties
vi
28 Conclusion
vii
31 Introduction
1907
32 Cholesterol Suppresses Kir2 Activity InVitro and InVivo
1908
33 Evidence for Specific SterolProtein Interactions in the Regulation of Kir Channels
1912
34 Structural Determinants of Cholesterol Sensitivity of Kir2 Channels
1915
35 Physiological Impact of CholesterolInduced Suppression of Kir2 Channels
1923
36 Concluding Remarks and Future Directions
1924
41 Introduction
1931
42 Molecular Components of SOCE
1932
43 Lipid Raft Domains and Caveolae
1935
44 The Role of Lipid Raft Domains in the Regulation of TRPC1
1937
45 Molecular Complexity in the Regulation of SOCE
1943
46 Conclusions
1944
51 Introduction
1955
53 Mechanisms of Cholesterol Effects on Ion Channels
1959
54 Cholesterol as a Target for Therapeutic Agents
1965
61 BK Channels and Steroids
1972
62 Conclusions
1988
Acknowledgments
1989
71 Potassium Channels in the Immune System
1998
72 Regulation of Potassium Channels by Membrane Cholesterol and Lipid Raft Microdomains
2000
73 Localization of Major VoltageDependent Kv13 and Kv15 Channels in CholesterolRich Membrane Microdomains in Leukocytes
2011
The Immunological Synapse
2014
Acknowledgments
2017
81 Introduction
2027
Structure and Multilayered Regulation
2029
98 A New CholesterolRecognition Motif in the AChR is also Present in GPCRs
2057
Acknowledgments
2062
101 Introduction
2070
102 Presence of CholesterolBinding Domains?
2071
103 Presence of CholesterolRich Microdomains?
2072
104 Alterations in Protein Function Induced by Changes in the Cholesterol Content in MembranesCells?
2075
105 Alterations in Receptor Function Following Substitution of Cholesterol by Sterol Analogs? Correlation of Receptor Function with Membrane Par...
2079
106 CholesterolBinding Molecules as Functional Cholesterol Competitors?
2081
107 Cholesterol Requirement for Heterologous Over Expression Solubilization and Purification of Receptors?
2083
108 Direct Interaction of the Receptor with Labeled Cholesterol Probes?
2084
109 Concluding Remarks
2088
111 Introduction
2098
112 GPCR Structural Biology Comes of Age
2100
113 Cholesterol is Physiologically Important
11-1
114 Gaining Insights into CholesterolGPCR Interactions
11-4
115 Structural Characterization of CholesterolBinding Site in Adrenergic Receptors
11-5
117 Direct Effect of Cholesterol on β2AR
11-6
119 Structural Insight on Stabilizing Effect of Cholesterol
11-9
1111 CholesterolBinding Site in the Crystal Structure of β1AR
11-11
1113 Conclusion
11-13
Acknowledgment
11-14
Structure and Membrane Organization
11-21
The Serotonin1A Receptor
11-25
123 Acute Versus Chronic Cholesterol Depletion
11-26
124 Cholesterol Binding Sites in GPCRs
11-31
Implications in Pathogen Entry
11-33
Acknowledgments
11-34
131 TollLike Receptor Signaling
11-41
132 Lipid Rafts and TLR Signaling
11-42
133 Summary
11-44
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About the author (2012)

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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