Pulmonary vascular K+ channel expression and vasoreactivity in a model of congenital heart disease.
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 (K Ca ) 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 K Ca 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, K Ca channel expression is increased and TASK is decreased.
Cornfield
David N
DN
Division of Pediatric Pulmonology and Critical Care Medicine, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA. cornf001@umn.edu
Resnik
Ernesto R
ER
Herron
Jean M
JM
Reinhartz
Olaf
O
Fineman
Jeffrey R
JR
D000471:Alkalosis / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001808:Blood Vessels / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D005333:Fetus / Q000502:physiology; D006330:Heart Defects, Congenital / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011652:Pulmonary Circulation / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051669:Shab Potassium Channels; D012756:Sheep; D014666:Vasomotor System / Q000503:physiopathology*
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D002118:Calcium