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Am J Physiol Lung Cell Mol Physiol 283: L1210-L1219, 2002. First published August 23, 2002; doi:10.1152/ajplung.00428.2001
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Vol. 283, Issue 6, L1210-L1219, December 2002

Pulmonary vascular K+ channel expression and vasoreactivity in a model of congenital heart disease

David N. Cornfield1, Ernesto R. Resnik1, Jean M. Herron1, Olaf Reinhartz2, and Jeffrey R. Fineman3

1 Division of Pediatric Pulmonology and Critical Care Medicine, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455; and 3 Departments of Pediatrics and 2 Cardiothoracic Surgery, University of California- San Francisco and Cardiovascular Research Institute, San Francisco, California 94143

K+ channels play an important role in mediating pulmonary vasodilation caused by increased oxygen tension, nitric oxide, alkalosis, and shear stress. To test the hypothesis that lung K+ channel gene expression may be altered by chronic increases in pulmonary blood flow, we measured gene and protein expression of calcium-sensitive (KCa) and voltage-gated (Kv2.1) K+ channels, and a pH-sensitive K+ channel (TASK), in distal lung from fetal lambs in which an aortopulmonary shunt was placed at 139 days gestation. Under baseline conditions, animals with an aortopulmonary shunt showed elevated pulmonary artery pressure and pulmonary blood flow compared with twin controls. Hypoxia caused a greater increase in pulmonary vascular tone in shunt animals compared with controls. Alkalosis caused pulmonary vasodilation in control but not shunt animals. To determine lung K+ channel mRNA levels, we performed quantitative RT-PCR. In comparison with control animals, lung KCa channel mRNA content was increased in shunt animals, whereas TASK mRNA levels were decreased. There was no difference in Kv2.1 mRNA levels. Channel protein expression was consistent with these findings. We conclude that, in the presence of elevated pulmonary blood flow, KCa channel expression is increased and TASK is decreased.

pH-sensitive potassium channel; pulmonary hypertension; calcium-sensitive potassium channel; vascular reactivity


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Am. J. Physiol. Heart Circ. Physiol.Home page
Z. Ghorishi, J. M. Milstein, F. R. Poulain, A. Moon-Grady, T. Tacy, S. H. Bennett, J. R. Fineman, and M. W. Eldridge
Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow
Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3006 - H3018.
[Abstract] [Full Text] [PDF]




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