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Am J Physiol Regulatory Integrative Comp Physiol 293 (1): 191-199

Copyright © 2007 by the American Physiological Society.

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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

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

Weiwei Shi, Ningren Cui, Yun Shi, Xiaoli Zhang, Yang Yang, , and Chun Jiang

Department of Biology, Georgia State University, Atlanta, Georgia

Received for publication 23 January 2007. Accepted for publication 30 March 2007.

ABSTRACT Back to Top

Abstract: Kir6.1/SUR2B channel is the major isoform of KATP 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 KATP 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 KATP channel opener pinacidil and inhibited by KATP 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 KATP 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 Gq-coupled V1a receptor and PKC.

Key Words: K+ channel • antagonist • second messenger • vascular tones • phosphorylation

Address for reprint requests and other correspondence: C. Jiang, Dept. of Biology, Georgia State Univ., 24 Peachtree Center Ave. Atlanta, GA 30302-4010 (e-mail: cjiang{at}gsu.edu)

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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J. Jiao, V. Garg, B. Yang, T. S. Elton, and K. Hu (2008)
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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.
A. R. Mackie, L. I. Brueggemann, K. K. Henderson, A. J. Shiels, L. L. Cribbs, K. E. Scrogin, and K. L. Byron (2008)
J. Pharmacol. Exp. Ther. 325, 475-483
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