HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/C440    most recent 00492.2006v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Tikku, S. Articles by Levitan, I. Search for Related Content PubMed PubMed Citation Articles by Tikku, S. Articles by Levitan, I.

VASCULAR BIOLOGY

Relationship between Kir2.1/Kir2.3 activity and their distributions between cholesterol-rich and cholesterol-poor membrane domains

¹Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania; ²Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; ³Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and ⁴Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York

Submitted 18 September 2006 ; accepted in final form 13 April 2007

Our earlier studies have shown that Kir2.x channels are suppressed by an increase in the level of cellular cholesterol, whereas cholesterol depletion enhances the activity of the channels. In this study, we show that Kir2.1 and Kir2.3 channels have double-peak distributions between cholesterol-rich (raft) and cholesterol-poor (non-raft) membrane fractions, indicating that the channels exist in two different types of lipid environment. We also show that whereas methyl--cyclodextrin-induced cholesterol depletion removes cholesterol from both raft and non-raft membrane fractions, cholesterol enrichment results in cholesterol increase exclusively in the raft fractions. Kinetics of both depletion-induced Kir2.1 enhancement and enrichment-induced Kir2.1 suppression correlate with the changes in the level of raft cholesterol. Furthermore, we show not only that cholesterol depletion shifts the distribution of the channels from cholesterol-rich to cholesterol-poor membrane fractions but also that cholesterol enrichment has the opposite effect. These observations suggest that change in the level of raft cholesterol alone is sufficient to suppress Kir2 activity and to facilitate partitioning of the channels to cholesterol-rich domains. Therefore, we suggest that partitioning to membrane rafts plays an important role in the sensitivity of Kir2 channels to cholesterol.

ion channels; inward rectifiers; inwardly rectifying potassium channels

This article has been cited by other articles:

				D. K. Singh, A. Rosenhouse-Dantsker, C. G. Nichols, D. Enkvetchakul, and I. Levitan Direct Regulation of Prokaryotic Kir Channel by Cholesterol J. Biol. Chem., October 30, 2009; 284(44): 30727 - 30736. [Abstract] [Full Text] [PDF]

				E. Balse, S. El-Haou, G. Dillanian, A. Dauphin, J. Eldstrom, D. Fedida, A. Coulombe, and S. N. Hatem Cholesterol modulates the recruitment of Kv1.5 channels from Rab11-associated recycling endosome in native atrial myocytes PNAS, August 25, 2009; 106(34): 14681 - 14686. [Abstract] [Full Text] [PDF]