2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2008040427v1 20/3/513    most recent 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, P. Articles by Wang, W.-H. Search for Related Content PubMed PubMed Citation Articles by Sun, P. Articles by Wang, W.-H.

Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct

Peng Sun^*, Wen Liu, Dao-Hong Lin^*, Peng Yue^*, Rowena Kemp^*, Lisa M. Satlin and Wen-Hui Wang^*

^* Department of Pharmacology, New York Medical College, Valhalla, and Department of Pediatrics, Mount Sinai School of Medicine, New York, New York

Correspondence: Dr. Wen-Hui Wang, Department of Pharmacology, BSB 537, New York Medical College, Valhalla, NY 10595. Phone: 914-594-4139; Fax: 914-347-4956; E-mail: wenhui_wang{at}nymc.edu

Received for publication April 25, 2008. Accepted for publication September 17, 2008.

The cortical collecting duct (CCD), which is involved in renal potassium (K) excretion, expresses cytochrome P450 (CYP)-epoxygenase. Here, we examined the effect of high dietary K on renal expression of CYP2C23 and CYP2J2 in the rat, as well as the role of CYP-epoxygenase–dependent metabolism of arachidonic acid in the regulation of Ca²⁺-activated big-conductance K (BK) channels. By Western blot analysis, high dietary K stimulated the expression of CYP2C23 but not CYP2J2 and increased 11,12-epoxyeicosatrienoic acid (11,12-EET) levels in isolated rat CCD tubules. Application of arachidonic acid increased BK channel activity, and this occurred to a greater extent in rats on a high-K diet compared with a normal-K diet. This effect was unlikely due to arachidonic acid–induced changes in membrane fluidity, because 11,14,17-eicosatrienoic acid did not alter BK channel activity. Inhibiting CYP-epoxygenase but not cyclooxygenase- or CYP--hydroxylase–dependent pathways completely abolished the stimulatory effect of arachidonic acid on BK channel activity. In addition, application of 11,12-EET mimicked the effect of arachidonic acid on BK channel activity, even in the presence of CYP-epoxygenase inhibition. This effect seemed specific to 11,12-EET, because both 8,9- and 14,15-EET failed to stimulate BK channels. Finally, inhibition of CYP-epoxygenase abolished iberiotoxin-sensitive and flow-stimulated but not basal net K secretion in isolated microperfused CCD. In conclusion, high dietary K stimulates the renal CYP-epoxygenase pathway, which plays an important role in activating BK channels and flow-stimulated K secretion in the CCD.

This article has been cited by other articles:

				E. L. Liclican, A. B. Doumad, J. Wang, J. Li, J. R. Falck, C. T. Stier Jr, and M. A. Carroll Inhibition of the Adenosine2A Receptor-Epoxyeicosatrienoic Acid Pathway Renders Dahl Salt-Resistant Rats Hypertensive Hypertension, December 1, 2009; 54(6): 1284 - 1290. [Abstract] [Full Text] [PDF]

				W. Liu, Y. Wei, P. Sun, W.-H. Wang, T. R. Kleyman, and L. M. Satlin Mechanoregulation of BK channel activity in the mammalian cortical collecting duct: role of protein kinases A and C Am J Physiol Renal Physiol, October 1, 2009; 297(4): F904 - F915. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673