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) Supplemental Figure All Versions of this Article: 293/1/R191    most recent 00047.2007v1 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 (4) Citing Articles via Google Scholar Google Scholar Articles by Shi, W. Articles by Jiang, C. Search for Related Content PubMed PubMed Citation Articles by Shi, W. Articles by Jiang, C.

REPORT

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Arginine vasopressin inhibits Kir6.1/SUR2B channel and constricts the mesenteric artery via V1a receptor and protein kinase C

Department of Biology, Georgia State University, Atlanta, Georgia

Submitted 23 January 2007 ; accepted in final form 30 March 2007

ABSTRACT

Kir6.1/SUR2B channel is the major isoform of K_ATP channels in the vascular smooth muscle. Genetic disruption of either subunit leads to dysregulation of vascular tone and regional blood flows. To test the hypothesis that the Kir6.1/SUR2B channel is a target molecule of arginine vasopressin (AVP), we performed studies on the cloned Kir6.1/SUR2B channel and cell-endogenous K_ATP channel in rat mesenteric arteries. The Kir6.1/SUR2B channel was expressed together with V1a receptor in the HEK-293 cell line. Whole cell currents of the transfected HEK cells were activated by K_ATP channel opener pinacidil and inhibited by K_ATP channel inhibitor glibenclamide. AVP produced a concentration-dependent inhibition of the pinacidil-activated currents with IC₅₀ 2.0 nM. The current inhibition was mediated by a suppression of the open-state probability without effect on single-channel conductance. An exposure to 100 nM PMA, a potent PKC activator, inhibited the pinacidil-activated currents, and abolished the channel inhibition by AVP. Such an effect was not seen with inactive phorbol ester. A pretreatment of the cells with selective PKC blocker significantly diminished the inhibitory effect of AVP. In acutely dissociated vascular smooth myocytes, AVP strongly inhibited the cell-endogenous K_ATP channel. In isolated mesenteric artery rings, AVP produced concentration-dependent vasoconstrictions with EC₅₀ 6.5 nM. At the maximum effect, pinacidil completely relaxed vasoconstriction in the continuing exposure to AVP. The magnitude of the AVP-induced vasoconstriction was significantly reduced by calphostin-C. These results therefore indicate that the Kir6.1/SUR2B channel is a target molecule of AVP, and the channel inhibition involves G_q-coupled V1a receptor and PKC.

K⁺ channel; antagonist; second messenger; vascular tones; phosphorylation

This article has been cited by other articles:

				J. Jiao, V. Garg, B. Yang, T. S. Elton, and K. Hu Protein Kinase C-{epsilon} Induces Caveolin-Dependent Internalization of Vascular Adenosine 5'-Triphosphate-Sensitive K+ Channels Hypertension, September 1, 2008; 52(3): 499 - 506. [Abstract] [Full Text] [PDF]

				A. R. Mackie, L. I. Brueggemann, K. K. Henderson, A. J. Shiels, L. L. Cribbs, K. E. Scrogin, and K. L. Byron Vascular KCNQ Potassium Channels as Novel Targets for the Control of Mesenteric Artery Constriction by Vasopressin, Based on Studies in Single Cells, Pressurized Arteries, and in Vivo Measurements of Mesenteric Vascular Resistance J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 475 - 483. [Abstract] [Full Text] [PDF]