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: 294/3/C765    most recent 00528.2007v1 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 (5) Citing Articles via Google Scholar Google Scholar Articles by Zhang, Y. Articles by Wang, W.-H. Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Wang, W.-H.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD

¹Department of Pharmacology, Harbin Medical University, Harbin, China; and ²Department of Pharmacology, New York Medical College, Valhalla, New York

Submitted 7 November 2007 ; accepted in final form 8 January 2008

We used Western blot analysis to examine the effect of dietary K intake on the expression of serine/threonine protein phosphatase in the kidney. K restriction significantly decreased the expression of catalytic subunit of protein phosphatase (PP)2B but increased the expression of PP2B regulatory subunit in both rat and mouse kidney. However, K depletion did not affect the expression of PP1 and PP2A. Treatment of M-1 cells, mouse cortical collecting duct (CCD) cells, or 293T cells with glucose oxidase (GO), which generates superoxide anions through glucose metabolism, mimicked the effect of K restriction on PP2B expression and significantly decreased expression of PP2B catalytic subunits. However, GO treatment increased expression of regulatory subunit of PP2B and had no effect on expression of PP1, PP2A, and protein tyrosine phosphatase 1D. Moreover, deletion of gp91-containing NADPH oxidase abolished the effect of K depletion on PP2B. Thus superoxide anions or related products may mediate the inhibitory effect of K restriction on the expression of PP2B catalytic subunit. We also used patch-clamp technique to study the effect of inhibiting PP2B on renal outer medullary K (ROMK) channels in the CCD. Application of cyclosporin A or FK506, inhibitors of PP2B, significantly decreased ROMK channels, and the effect of PP2B inhibitors was abolished by blocking p38 mitogen-activated protein kinase (MAPK) and ERK. Furthermore, Western blot demonstrated that inhibition of PP2B with cyclosporin A or small interfering RNA increased the phosphorylation of ERK and p38 MAPK. We conclude that K restriction suppresses the expression of PP2B catalytic subunits and that inhibition of PP2B decreases ROMK channel activity through stimulation of MAPK in the CCD.

potassium depletion; p38 mitogen-activated protein kinase; extracellular signal-regulated kinase 1/2; potassium secretion

This article has been cited by other articles:

				S. Laycock, H. C. Taylor, C. Haigh, A. T. Lee, G. J. Cooper, A. C. M. Ong, and L. Robson A novel dephosphorylation-activated conductance in a mouse renal collecting duct cell line Exp Physiol, August 1, 2009; 94(8): 914 - 927. [Abstract] [Full Text] [PDF]

				M. Greenlee, C. S. Wingo, A. A. McDonough, J.-H. Youn, and B. C. Kone Narrative Review: Evolving Concepts in Potassium Homeostasis and Hypokalemia Ann Intern Med, May 5, 2009; 150(9): 619 - 625. [Abstract] [Full Text] [PDF]

				K. Wang, Y. Song, D.-B. Chen, and J. Zheng Protein Phosphatase 3 Differentially Modulates Vascular Endothelial Growth Factor- and Fibroblast Growth Factor 2-Stimulated Cell Proliferation and Signaling in Ovine Fetoplacental Artery Endothelial Cells Biol Reprod, October 1, 2008; 79(4): 704 - 710. [Abstract] [Full Text] [PDF]