This Article Full Text Full Text (PDF) All Versions of this Article: 2003-0386OCv1 31/3/337    most recent Alert me when this article is cited Alert me if a correction is posted Services 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 Hong, Z. Articles by Olschewski, A. Search for Related Content PubMed PubMed Citation Articles by Hong, Z. Articles by Olschewski, A.

Subacute Hypoxia Decreases Voltage-Activated Potassium Channel Expression and Function in Pulmonary Artery Myocytes

VA Medical Center, University of Minnesota, Minneapolis, Minnesota; and Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig-University, Giessen, Germany

Address correspondence to: Andrea Olschewski, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig-University, D-35392 Giessen, Germany. E-mail: andrea.j.olschewski{at}physiologie.med.uni-giessen.de

Chronic hypoxia results in both structural changes in the pulmonary artery and a sustained increase in pulmonary vascular tone. This study investigated the effects of subacute moderate hypoxia on expression and function of potassium (K⁺) channels in rat pulmonary artery myocytes (PASMCs). The rats were kept at 0.67 atmospheres for 6, 12, or 24 h. We found that the expression of mRNA for voltage-activated K⁺ channels (Kv)1.2, Kv1.5, and Kv2.1 is reduced after less than 24 h of this moderate hypoxia. K⁺ current (Ik) is significantly inhibited in PASMCs from rats hypoxic for 24 h, resting membrane potential is depolarized and cytosolic [Ca²⁺] is increased in these cells. In addition, antibodies to Kv1.2, Kv1.5, and Kv2.1 inhibit Ik, cause membrane depolarization and attenuate both hypoxia- and 4-AP–induced elevation in [Ca²⁺]_i in PASMCs from normoxic rats but not from 24 h hypoxic rats. Subacute hypoxia does not completely remove the mRNA for Kv1.2, Kv1.5, and Kv2.1, but antibodies against these channels no longer alter Ik or cytosolic calcium, suggesting that subacute hypoxia may inactivate the channels as well as reduce expression. As the expression of mRNA for Kv1.2, Kv1.5, and Kv2.1 is sensitive to subacute hypoxia and decreased expression/function of these channels has physiologic effects on membrane potential and cytosolic calcium, it seems likely that these Kv channels may also be involved in the mechanism of high-altitude pulmonary edema and possibly in the signaling of chronic hypoxic pulmonary hypertension.

Abbreviations: 4-aminopiridine, 4-AP • ethylene glycol-bis(ß-aminoethyl ether) N,N,N',N'-tetraacetic acid, EGTA • resting membrane potential, E_m • high-altitude pulmonary edema, HAPE • N-(2-hydroxyethyl)-piperazine-N'-(2-ethane sulfonic acid), HEPES • hypoxic pulmonary vasoconstriction, HPV • potassium current, Ik • inward-rectifier potassium channel, Kir • voltage-activated potassium channels, Kv • optical density, OD • pulmonary artery, PA • rat pulmonary artery myocytes, PASMCs • polymerase chain reaction, PCR • reverse transcriptase, RT

This article has been cited by other articles:

				L. Stirling, M. R. Williams, and A. D. Morielli Dual Roles for RHOA/RHO-Kinase In the Regulated Trafficking of a Voltage-sensitive Potassium Channel Mol. Biol. Cell, June 15, 2009; 20(12): 2991 - 3002. [Abstract] [Full Text] [PDF]

				V. Jakoubek, J. Bibova, J. Herget, and V. Hampl Chronic hypoxia increases fetoplacental vascular resistance and vasoconstrictor reactivity in the rat Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1638 - H1644. [Abstract] [Full Text] [PDF]

				E. C. Connors, B. A. Ballif, and A. D. Morielli Homeostatic Regulation of Kv1.2 Potassium Channel Trafficking by Cyclic AMP J. Biol. Chem., February 8, 2008; 283(6): 3445 - 3453. [Abstract] [Full Text] [PDF]

				E. M. Whitman, S. Pisarcik, T. Luke, M. Fallon, J. Wang, J. T. Sylvester, G. L. Semenza, and L. A. Shimoda Endothelin-1 mediates hypoxia-induced inhibition of voltage-gated K+ channel expression in pulmonary arterial myocytes Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L309 - L318. [Abstract] [Full Text] [PDF]

				M. Marino, J. L. Beny, A. C. Peyter, R. Bychkov, G. Diaceri, and J. F. Tolsa Perinatal hypoxia triggers alterations in K+ channels of adult pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1171 - L1182. [Abstract] [Full Text] [PDF]

				C. D. Fike, M. R. Kaplowitz, Y. Zhang, and J. A. Madden Voltage-gated K+ channels at an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1169 - L1176. [Abstract] [Full Text] [PDF]

				E. K. Weir and A. Olschewski Role of ion channels in acute and chronic responses of the pulmonary vasculature to hypoxia Cardiovasc Res, September 1, 2006; 71(4): 630 - 641. [Abstract] [Full Text] [PDF]

				A. Olschewski, Y. Li, B. Tang, J. Hanze, B. Eul, R. M. Bohle, J. Wilhelm, R. E. Morty, M. E. Brau, E. K. Weir, et al. Impact of TASK-1 in Human Pulmonary Artery Smooth Muscle Cells Circ. Res., April 28, 2006; 98(8): 1072 - 1080. [Abstract] [Full Text] [PDF]

				O. Platoshyn, E. E. Brevnova, E. D. Burg, Y. Yu, C. V. Remillard, and J. X.-J. Yuan Acute hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells Am J Physiol Cell Physiol, March 1, 2006; 290(3): C907 - C916. [Abstract] [Full Text] [PDF]

				J. Wang, L. Weigand, W. Wang, J. T. Sylvester, and L. A. Shimoda Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1049 - L1058. [Abstract] [Full Text] [PDF]