Cholesterol and Ion Channels

Levitan, Irena; Fang, Yun; Rosenhouse-Dantsker, Avia; Romanenko, Victor

doi:10.1007/978-90-481-8622-8_19

Cited by 247Lipid Membrane Structure and BehaviorIon channel regulation and functionCaveolin-1 and cellular processes

Cholesterol and Ion Channels

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Levitan, Irena, Fang, Yun, Rosenhouse-Dantsker, Avia, Romanenko, Victor·2010·Subcellular Biochemistry

DOI 10.1007/978-90-481-8622-8_19PMC PMC2895485

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Abstract

A variety of ion channels, including members of all major ion channel families, have been shown to be regulated by changes in the level of membrane cholesterol and partition into cholesterol-rich membrane domains. In general, several types of cholesterol effects have been described. The most common effect is suppression of channel activity by an increase in membrane cholesterol, an effect that was described for several types of inwardly-rectifying K(+) channels, voltage-gated K(+) channels, Ca(+2) sensitive K(+) channels, voltage-gated Na(+) channels, N-type voltage-gated Ca(+2) channels and volume-regulated anion channels. In contrast, several types of ion channels, such as epithelial amiloride-sensitive Na(+) channels and Transient Receptor Potential channels, as well as some of the types of inwardly-rectifying and voltage-gated K(+) channels were shown to be inhibited by cholesterol depletion. Cholesterol was also shown to alter the kinetic properties and current-voltage dependence of several voltage-gated channels. Finally, maintaining membrane cholesterol level is required for coupling ion channels to signalling cascades. In terms of the mechanisms, three general mechanisms have been proposed: (i) specific interactions between cholesterol and the channel protein, (ii) changes in the physical properties of the membrane bilayer and (iii) maintaining the scaffolds for protein-protein interactions. The goal of this review is to describe systematically the role of cholesterol in regulation of the major types of ion channels and to discuss these effects in the context of the models proposed.

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In addition to inhibiting ABCA1 function in cholesterol efflux, the biased membrane lipid composition potentially interferes with functions of several channels on the membrane directly or by altering bilayer stiffness and hydrophobic mismatch.
“In addition to inhibiting ABCA1 function in cholesterol efflux, the biased membrane lipid composition potentially interferes with functions of several channels on the membrane directly or by altering bilayer stiffness and hydrophobic mismatch between transmembrane domains and the lipid bilayer69.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [69]
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Enhanced role of potassium channels in relaxations to acetylcholine in hypercholesterolemic rabbit carotid artery
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Caveolae Localize Protein Kinase A Signaling to Arterial ATP-Sensitive Potassium Channels
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Cholesterol Antagonizes Ethanol Potentiation of Human Brain BKCa Channels Reconstituted into Phospholipid Bilayers
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Diversity of Cl− Channels
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Differential Recruitment of Kv1.4 and Kv4.2 to Lipid Rafts by PSD-95
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Hypercholesterolemia Suppresses Inwardly Rectifying K + Channels in Aortic Endothelium In Vitro and In Vivo
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Identification of a C-terminus domain critical for the sensitivity of Kir2.1 to cholesterol
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Swelling‐activated ion channels: functional regulation in cell‐swelling, proliferation and apoptosis
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Ceramide inhibits the potassium channel Kv1.3 by the formation of membrane platforms
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Potassium Channels in the Human Myometrium
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Assembly and Trafficking of a Multiprotein ROMK (Kir 1.1) Channel Complex by PDZ Interactions
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Depletion of membrane cholesterol eliminates the Ca2+‐activated component of outward potassium current and decreases membrane capacitance in rat uterine myocytes
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Localization of Ion Channels to Lipid Raft Domains within the Cardiovascular System
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Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes
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BK Channels Are Linked to Inositol 1,4,5-Triphosphate Receptors via Lipid Rafts
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The Neural Cell Adhesion Molecule Regulates Cell-Surface Delivery of G-Protein-Activated Inwardly Rectifying Potassium Channels Via Lipid Rafts
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Partial restoration of cAMP-stimulated CFTR chloride channel activity in ΔF508 cells by deoxyspergualin
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Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes
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β2 and β4 Subunits of BK Channels Confer Differential Sensitivity to Acute Modulation by Steroid Hormones
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Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin
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Caveolin-1 Expression and Membrane Cholesterol Content Modulate N-Type Calcium Channel Activity in NG108-15 Cells
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Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to adenosine-mediated relaxation in porcine coronary arterioles
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CFTR in a lipid raft-TNFR1 complex modulates gap junctional intercellular communication and IL-8 secretion
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Cutting Edge: Optical Microspectrophotometry Supports the Existence of Gel Phase Lipid Rafts at the Lamellipodium of Neutrophils: Apparent Role in Calcium Signaling
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The Epithelial Sodium Channel (ENaC) Traffics to Apical Membrane in Lipid Rafts in Mouse Cortical Collecting Duct Cells
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Neuronal fusion pore assembly requires membrane cholesterol
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Membrane Cholesterol Regulates Smooth Muscle Phasic Contraction
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Swelling-Induced Taurine Transport: Relationship with Chloride Channels, Anion-Exchangers and Other Swelling-Activated Transport Pathways
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Inhibition of Volume-Regulated Anion Channels by Dominant-Negative Caveolin-1
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Cellular cholesterol controls TRPC3 function: evidence from a novel dominant-negative knockdown strategy
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A role for hTRPC1 and lipid raft domains in store-mediated calcium entry in human platelets
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TRPC channel lipid specificity and mechanisms of lipid regulation
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Bilayer Thickness Modulates the Conductance of the BK Channel in Model Membranes
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The Activity of the Epithelial Sodium Channels Is Regulated by Caveolin-1 via a Nedd4-2-dependent Mechanism
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Relationship between Kir2.1/Kir2.3 activity and their distributions between cholesterol-rich and cholesterol-poor membrane domains
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cAMP-induced Cytoskeleton Rearrangement Increases Calcium Transients through the Enhancement of Capacitative Calcium Entry
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Membrane cholesterol modulates dihydropyridine receptor function in mice fetal skeletal muscle cells
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Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO
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Targeting of Voltage-Gated K + and Ca 2+ Channels and Soluble N -Ethylmaleimide-Sensitive Factor Attachment Protein Receptor Proteins to Cholesterol-Rich Lipid Rafts in Pancreatic α-Cells: Effects on Glucagon Stimulus-Secretion Coupling
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TRPC1 is regulated by caveolin‐1 and is involved in oxidized LDL‐induced apoptosis of vascular smooth muscle cells
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Identification of yeast proteins necessary for cell-surface function of a potassium channel
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Caveolin Regulates Kv1.5 Trafficking to Cholesterol-Rich Membrane Microdomains
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Estrogen Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator-Mediated Chloride Secretion
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Cholesterol modulates cell signaling and protein networking by specifically interacting with PDZ domain-containing scaffold proteins
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An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis
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Authors: Levitan, I., Fang, Y., Rosenhouse-Dantsker, A., & Romanenko, V.
Affiliations: University of Illinois Chicago (US)
University of Pennsylvania (US)
University of Rochester Medicine (US)
Corresponding author: Levitan, Irena
ORCID: Levitan, Irena
Fang, Yun
Venue: Subcellular Biochemistry
Publisher: Springer Netherlands
Published: 2010
Volume: 51
Pages: 509-549
ISSN: 0306-0225 (ISSN-L)
DOI: 10.1007/978-90-481-8622-8_19
PMC: PMC2895485
OpenAlex: W1497754562
Cited by: 247
References: 213
Citations by year: 2026: 17 · 2025: 17 · 2024: 14 · 2023: 16 · 2022: 26 · 2021: 19 · 2020: 11 · 2019: 14 · 2018: 9 · 2017: 12 · 2016: 7 · 2015: 10 · 2014: 21 · 2013: 15 · 2012: 17
FWCI: 20.98
Type: book chapter
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Sub-cellular biochemistry/Subcellular biochemistry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL073965, HL073965, R01HL083298, HL-083298)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords: membrane cholesterol, ion channel modulation, cholesterol-rich membrane domains, inwardly rectifying potassium channels, voltage-gated potassium channels, voltage-gated sodium channels, N-type calcium channels, volume-regulated anion channel, amiloride-sensitive sodium channel, TRP channels, cholesterol depletion, channel kinetics
MeSH terms: Animals, Cholesterol, Humans, Hypercholesterolemia, Ion Channels, Membrane Lipids, Molecular Conformation, Calcium Channels, Sodium Channels, Signal Transduction, Ion Channel Gating, Chloride Channels, Membrane Microdomains, Potassium Channels, Voltage-Gated, Potassium Channels, Inwardly Rectifying, Potassium Channels, Calcium-Activated, TRPC Cation Channels

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