Oxygen Tension Modulates the Expression of Pulmonary Vascular Bkca Channel Alpha- and Beta-subunits.
From: Univ. of Minnesota, Minneapolis, MN 55455, USA. resni004@umn.edu
American journal of physiology. Lung cellular and molecular physiology
- Publish Date: Apr 2006
- ISSN: 1040-0605
- Volume: 290
- Issue: 4
- Pages: L761-L768
- Medium: Print
- Language: English
- Citation (JAMA): Resnik Ernesto, Herron Jean, Fu Rao, et al. Oxygen Tension Modulates the Expression of Pulmonary Vascular Bkca Channel Alpha- and Beta-subunits.. Am. J. Physiol. Lung Cell Mol. Physiol. Apr 2006;290:L761-L768
Abstract
At birth, the lung environment changes from low to relatively high O(2) tension. Pulmonary blood flow increases and pulmonary artery pressure decreases. Recent data suggest that pulmonary vascular calcium-sensitive K(+) channel (BK(Ca)) activation mediates perinatal pulmonary vasodilation. Although BK(Ca) channel expression is developmentally regulated, the molecular mechanisms responsible for BK(Ca) expression remain unknown. We tested the hypothesis that the low-O(2) tension environment of the normal fetus modulates BK(Ca) channel expression. We analyzed BK(Ca) expression under conditions of hypoxia and normoxia both in vitro and in vivo. BK(Ca) alpha-subunit mRNA expression increased twofold in ovine pulmonary artery smooth muscle cell (PASMC) primary cultures maintained in hypoxia. In vivo, BK(Ca) expression was similarly affected by hypoxia. When adult Sprague-Dawley rats were placed in hypobaric hypoxic chambers for 3 wk, hypoxic animals showed an increase of threefold in the expression of BK(Ca) alpha- and more than twofold in the expression of BK(Ca) beta(1)-subunit mRNA. Immunochemical staining was consistent with the genetic data. To assess transcriptional activation of the beta-subunit of the BK(Ca), both BK(Ca) beta(1)- and beta(2)-subunit luciferase (K(Ca) beta:luc(+)) reporter genes were constructed. Hypoxia increased PASMC K(Ca) beta(1):luc(+) reporter expression by threefold and K(Ca) beta(2):luc(+) expression by 35%. Fetal PASMC treated with the hypoxia-inducible factor-1 mimetic deferoxamine showed a 63 and 41% increase in BK(Ca) channel alpha- and beta(1)-subunit expression, respectively. Together, these results suggest that oxygen tension modulates BK(Ca) channel subunit mRNA expression, and the regulation is, at least in part, at the transcriptional level.
Mesh Headings (Keywords): Animals, Anoxia, Calcium, Cells, Cultured, Deferoxamine, Fetus, Immunohistochemistry, Intracellular Membranes, Large-Conductance Calcium-Activated Potassium Channels, Lung, Myocytes, Smooth Muscle, Osmolar Concentration, Oxygen, Partial Pressure, Peptides, Protein Isoforms, Pulmonary Artery, Rats, Rats, Sprague-Dawley, Sheep, Transcription, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 16284215
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