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: 287/2/H533    most recent 00228.2003v1 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 ISI 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 ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Wang, G.-X. Articles by Yamboliev, I. A. Search for Related Content PubMed PubMed Citation Articles by Wang, G.-X. Articles by Yamboliev, I. A.

Hypotonic activation of volume-sensitive outwardly rectifying chloride channels in cultured PASMCs is modulated by SGK

Ge-Xin Wang,¹ Cian McCrudden,¹ Yan-Ping Dai,¹ Burton Horowitz,^2, Joseph R. Hume,¹ and Ilia A. Yamboliev¹

Departments of ¹ Pharmacology, and ² Physiology and Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, Nevada 89557-0270

Submitted 14 March 2003 ; accepted in final form 6 April 2004

The serum- and glucocorticoid-inducible kinase (SGK) is a serine/threonine protein kinase (PK) transcriptionally regulated by corticoids, serum, and cell volume. SGK regulates cell volume of various cells by effects on Na⁺ and K⁺ transport through membrane channels. We hypothesized a role for SGK in the activation of volume-sensitive osmolyte and anion channels (VSOACs) in cultured canine pulmonary artery smooth muscle cells (PASMCs). Intracellular dialysis through the patch electrode of recombinant active SGK, but not kinase-dead 60-SGK-K127M, heat-inactivated SGK, or active Akt1, partially activated VSOACs under isotonic conditions. Dialysis of active SGK before cell exposure to hypotonic medium significantly accelerated the activation kinetics and increased the maximal density of VSOAC current. Exposure of PASMCs to hypotonic medium (230 mosM) activated phosphatidylinositol 3-kinases (PI3Ks) and their downstream targets Akt/PKB and SGK but not PKC-. Inhibition of PI3Ks with wortmannin reduced the activation rate and maximal amplitude of VSOACs. Immunoprecipitated ClC-3 channels were phosphorylated by PKC- but not by SGK in vitro, suggesting that SGK may activate VSOACs indirectly. These data indicate that the PI3K-SGK cascade is activated on hypotonic swelling of PASMCs and, in turn, affects downstream signaling molecules linked to activation of VSOACs.

hypotonic cell swelling; Cl^– conductance; phosphatidylinositol 3-kinase; Akt/protein kinase B; protein kinase C-; pulmonary artery smooth muscle cells; volume-sensitive osmolyte and anion channels; serum- and glucocorticoid-inducible kinase

This article has been cited by other articles:

				Z. Ren, F. J. Raucci Jr., D. M. Browe, and C. M. Baumgarten Regulation of swelling-activated Cl- current by angiotensin II signalling and NADPH oxidase in rabbit ventricle Cardiovasc Res, January 1, 2008; 77(1): 73 - 80. [Abstract] [Full Text] [PDF]

				F. Lang, C. Bohmer, M. Palmada, G. Seebohm, N. Strutz-Seebohm, and V. Vallon (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms. Physiol Rev, October 1, 2006; 86(4): 1151 - 1178. [Abstract] [Full Text] [PDF]

				D. M. Browe and C. M. Baumgarten EGFR Kinase Regulates Volume-sensitive Chloride Current Elicited by Integrin Stretch via PI-3K and NADPH Oxidase in Ventricular Myocytes J. Gen. Physiol., February 27, 2006; 127(3): 237 - 251. [Abstract] [Full Text] [PDF]