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Channels (Austin)
2010 Jan 01;41:63-6. doi: 10.4161/chan.4.1.10366.
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Comparative analysis of cholesterol sensitivity of Kir channels: role of the CD loop.
Rosenhouse-Dantsker A
,
Leal-Pinto E
,
Logothetis DE
,
Levitan I
.
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Kir channels are important in setting the resting membrane potential and modulating membrane excitability. A common feature of Kir2 channels and several other ion channels that has emerged in recent years is that they are regulated by cholesterol, a major lipid component of the plasma membrane whose excess is associated with multiple pathological conditions. Yet, the mechanism by which cholesterol affects channel function is not clear. We have recently shown that the sensitivity of Kir2 channels to cholesterol depends on residues in the CD loop of the cytosolic domain of the channels with one of the mutations, L222I, abrogating cholesterol sensitivity of the channels completely. Here we show that in addition to Kir2 channels, members of other Kir subfamilies are also regulated by cholesterol. Interestingly, while similarly to Kir2 channels, several Kir channels, Kir1.1, Kir4.1 and Kir6.2Delta36 were suppressed by an increase in membrane cholesterol, the function of Kir3.4* and Kir7.1 was enhanced following cholesterol enrichment. Furthermore, we show that independent of the impact of cholesterol on channel function, mutating residues in the corresponding positions of the CD loop in Kir2.1 and Kir3.4*, inhibits cholesterol sensitivity of Kir channels, thus extending the critical role of the CD loop beyond Kir2 channels.
Ambudkar,
Cellular domains that contribute to Ca2+ entry events.
2004, Pubmed
Ambudkar,
Cellular domains that contribute to Ca2+ entry events.
2004,
Pubmed
Bolotina,
Variations of membrane cholesterol alter the kinetics of Ca2(+)-dependent K+ channels and membrane fluidity in vascular smooth muscle cells.
1989,
Pubmed
Bowles,
Hypercholesterolemia inhibits L-type calcium current in coronary macro-, not microcirculation.
2004,
Pubmed
Delling,
The neural cell adhesion molecule regulates cell-surface delivery of G-protein-activated inwardly rectifying potassium channels via lipid rafts.
2002,
Pubmed
,
Xenbase
Epshtein,
Identification of a C-terminus domain critical for the sensitivity of Kir2.1 to cholesterol.
2009,
Pubmed
Genda,
K(ATP) channel opening is an endogenous mechanism of protection against the no-reflow phenomenon but its function is compromised by hypercholesterolemia.
2002,
Pubmed
Heaps,
Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to adenosine-mediated relaxation in porcine coronary arterioles.
2005,
Pubmed
Hibino,
Distinct detergent-resistant membrane microdomains (lipid rafts) respectively harvest K(+) and water transport systems in brain astroglia.
2007,
Pubmed
Inanobe,
Structural diversity in the cytoplasmic region of G protein-gated inward rectifier K+ channels.
2007,
Pubmed
Kellner-Weibel,
Cytotoxic cholesterol is generated by the hydrolysis of cytoplasmic cholesteryl ester and transported to the plasma membrane.
1999,
Pubmed
Kruth,
Lipoprotein cholesterol and atherosclerosis.
2001,
Pubmed
Levitan,
Cholesterol and Kir channels.
2009,
Pubmed
Levitan,
Membrane cholesterol content modulates activation of volume-regulated anion current in bovine endothelial cells.
2000,
Pubmed
Lockwich,
Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains.
2000,
Pubmed
Lundbaek,
Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol.
2004,
Pubmed
Lundbaek,
Membrane stiffness and channel function.
1996,
Pubmed
Maguy,
Involvement of lipid rafts and caveolae in cardiac ion channel function.
2006,
Pubmed
Martens,
Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae.
2001,
Pubmed
Martens,
Differential targeting of Shaker-like potassium channels to lipid rafts.
2000,
Pubmed
Mathew,
Altered effects of potassium channel modulation in the coronary circulation in experimental hypercholesterolemia.
2001,
Pubmed
Nishida,
Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
2002,
Pubmed
Nishida,
Crystal structure of a Kir3.1-prokaryotic Kir channel chimera.
2007,
Pubmed
Pegan,
Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification.
2005,
Pubmed
,
Xenbase
Reimann,
Inwardly rectifying potassium channels.
1999,
Pubmed
Romanenko,
Modulation of endothelial inward-rectifier K+ current by optical isomers of cholesterol.
2002,
Pubmed
Romanenko,
Sensitivity of volume-regulated anion current to cholesterol structural analogues.
2004,
Pubmed
Romanenko,
Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels.
2004,
Pubmed
Ross,
Atherosclerosis--an inflammatory disease.
1999,
Pubmed
Shlyonsky,
Epithelial sodium channel activity in detergent-resistant membrane microdomains.
2003,
Pubmed
,
Xenbase
Steinberg,
Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime.
2002,
Pubmed
Toselli,
Caveolin-1 expression and membrane cholesterol content modulate N-type calcium channel activity in NG108-15 cells.
2005,
Pubmed
Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase
Vivaudou,
Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants.
1997,
Pubmed
,
Xenbase
Wu,
The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte.
1995,
Pubmed
Yeagle,
Cholesterol and the cell membrane.
1985,
Pubmed
Yeagle,
Modulation of membrane function by cholesterol.
1991,
Pubmed
