Comparative analysis of cholesterol sensitivity of Kir channels: role of the CD loop.

Channels
Avia Rosenhouse-DantskerIrena Levitan

Abstract

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 sensi...Continue Reading

Citations

Jan 11, 2012·Nature Structural & Molecular Biology·Vassiliy N BavroStephen J Tucker
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Dec 20, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Gregory B KowalskyIrena Levitan
Jul 20, 2014·The Journal of Physiology·Huazhi HanIrena Levitan
Dec 18, 2014·Biophysical Journal·Oliver FürstNazzareno D'Avanzo
Jan 20, 2011·Biophysical Journal·Avia Rosenhouse-DantskerIrena Levitan
Jul 22, 2015·Biochimica Et Biophysica Acta·Anna N BukiyaAvia Rosenhouse-Dantsker
Jul 30, 2011·Biochimica Et Biophysica Acta·Dev K SinghIrena Levitan
Nov 15, 2011·Molecular Genetics and Metabolism·Bikash R PattnaikDe-Ann M Pillers
Nov 20, 2014·Computational and Structural Biotechnology Journal·Avia Rosenhouse-DantskerIrena Levitan
Feb 2, 2011·Biophysical Journal·Wayland W L ChengColin G Nichols
Nov 14, 2018·Journal of Lipid Research·Anna N BukiyaAvia Rosenhouse-Dantsker
Oct 29, 2014·Journal of the American Society of Nephrology : JASN·Bing-Chen LiuHe-Ping Ma
Sep 11, 2013·The Journal of Biological Chemistry·Avia Rosenhouse-DantskerIrena Levitan
Feb 19, 2017·The Journal of Biological Chemistry·Anna N BukiyaAvia Rosenhouse-Dantsker
Feb 23, 2018·Lipid Insights·Avia Rosenhouse-Dantsker
Mar 1, 2021·Biophysical Journal·Brennica MarlowJens Meiler
Apr 5, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Florina ZakanyZoltan Varga
Aug 14, 2021·The Journal of General Physiology·Ida BjörkgrenPolina V Lishko
Aug 26, 2021·Cell Reports·Yamuna Kalyani MathiharanPaul A Slesinger

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