This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jackson, W. F. Search for Related Content PubMed PubMed Citation Articles by Jackson, W. F. Related Collections Related Article

(Circulation Research. 2006;98:982.)
© 2006 American Heart Association, Inc.

Editorials

Silent Inward Rectifier K⁺ Channels in Hypercholesterolemia

William F. Jackson

From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Mich.

Correspondence to William F. Jackson, PhD, Department of Pharmacology and Toxicology, Michigan State University, B420 Life Sciences Bldg, East Lansing, MI 48824. E-mail jacks783@msu.edu

See related article, pages 1064–1071

Key Words: hypercholesterolemia • potassium channels • inward rectifier potassium channels • arterioles • resistance arteries • cholesterol • lipid rafts

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Hypercholesterolemia is an independent risk factor for development of cardiovascular disease¹ and has been demonstrated to impair endothelium-dependent and independent vasodilatation.² However, the mechanisms responsible for changes in vascular reactivity and impaired blood flow regulation induced by hypercholesterolemia remain unclear. Previous studies in cultured endothelial cells have shown that cholesterol impairs whole-cell K_IR currents.³ Levitan and colleagues⁴ in this issue of Circulation Research extend these findings to show that exposure of endothelial cells to pathophysiologically relevant concentrations of acetylated low density lipoprotein (LDL) or very low density lipoprotein (vLDL) leads to membrane cholesterol enrichment, and also inhibits endothelial K_IR channel currents and shear stress–induced activation of these channels. More importantly, the authors show, for the first time, that in freshly isolated endothelial cells from hypercholesterolemic pigs, K_IR channel currents are impaired, and that this inhibition can be reversed by methyl-ß-cyclodextrin. Thus, hypercholesterolemia can be added to the list of pathophysiological states that appear to inhibit the function of vascular K_IR channels, including hypertension and diabetes.⁵ What remains unclear is the mechanism by which elevated membrane cholesterol silences endothelial K_IR channels, the generality of these findings to K_IR channels expressed in vascular smooth muscle cells, and the significance of cholesterol modulation of endothelial or smooth muscle K_IR channels in resistance arteries and arterioles, vessels that participate in the regulation of blood pressure and blood flow.

A number of ion channels, in addition to K_IR channels,⁶ appear to associate with cholesterol-rich lipid rafts, and changes in membrane cholesterol content have been shown . . . [Full Text of this Article]

Related Article:

Hypercholesterolemia Suppresses Inwardly Rectifying K⁺ Channels in Aortic Endothelium In Vitro and In Vivo

Yun Fang, Emile R. Mohler, III, Esther Hsieh, Hashim Osman, Seyed M. Hashemi, Peter F. Davies, George H. Rothblat, Robert L. Wilensky, and Irena Levitan
Circ. Res. 2006 98: 1064-1071. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				C. E. Hill Inward rectification and vascular function: As it was in the beginning J. Physiol., March 15, 2008; 586(6): 1465 - 1467. [Full Text] [PDF]