Pulmonary vascular response to normoxia and K(Ca) channel activity is developmentally regulated.
Pulmonary vascular response to normoxia and K(Ca) channel activity is developmentally regulated.
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DOI：
10.1152/ajplung.2001.280.6.l1250
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发表时间：
2001-06
期刊：
影响因子：
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通讯作者：
Michael T. Rhodes;V. Porter;C. Saqueton;J. Herron;E. Resnik;D. Cornfield
中科院分区：
文献类型：
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作者：
Michael T. Rhodes;V. Porter;C. Saqueton;J. Herron;E. Resnik;D. Cornfield
为了阐明肺血管氧传感的发育调节，我们测试了以下假设：1）胎儿而不是成人肺动脉平滑肌细胞（PASMC）可以直接感知氧的急性增加，2）Ca 2+敏感性K（+）（K（Ca））通道活性随成熟而降低，3）PASMC K（Ca）通道表达随成熟而降低。我们用荧光显微镜证实胎儿PASMCs而不是成人PASMCs能够感觉到O（2）张力的急性增加。急性常氧可使胎儿PASMCs胞浆Ca ~（2+）浓度（[Ca ~（2+）]（i））下降22 ± 2%，而成人PASMCs胞浆[Ca ~（2+）]（i）无明显变化（P < 0.01）。本文研究了钾通道拮抗剂对胎儿和成人PASMC [Ca ~（2+）]（i）的影响。Iberiotoxin（10（-9）M）可使胎儿PASMC（[Ca ~（2+）]（i））增加694 +/- 22%，而对成人PASMC无影响。本研究检测了胚胎和成年绵羊肺动脉远端钾（钙）通道的表达和mRNA水平。随着成熟，肺血管远端K（Ca）通道蛋白和mRNA表达均下降。我们的结论是，PASMCO（2）感应的成熟依赖性变化使得胎儿PASMCs在生物学关键时间点对O（2）张力的急性增加特别敏感。
To address developmental regulation of pulmonary vascular O(2) sensing, we tested the hypotheses that 1) fetal but not adult pulmonary artery smooth muscle cells (PASMCs) can directly sense an acute increase in O(2), 2) Ca2+-sensitive K(+) (K(Ca)) channel activity decreases with maturation, and 3) PASMC K(Ca) channel expression decreases with maturation. We used fluorescence microscopy to confirm that fetal but not adult PASMCs are able to sense an acute increase in O(2) tension. Acute normoxia induced a 22 +/- 2% decrease in cytosolic Ca2+ concentration ([Ca2+](i)) in fetal PASMCs and no change in ([Ca2+](i)) in adult PASMCs (P < 0.01). The effects of K(+) channel antagonists were studied on fetal and adult PASMC ([Ca2+](i)). Iberiotoxin (10(-9) M) caused PASMC ([Ca2+](i)) to increase by 694 +/- 22% in the fetus and caused no change in adult PASMCs. K(Ca) channel expression and mRNA levels in distal pulmonary arteries from fetal and adult sheep were examined. Both K(Ca) channel protein and mRNA expression in the distal pulmonary vasculature decreased with maturation. We conclude that maturation-dependent changes in PASMC O(2) sensing render the fetal PASMCs uniquely sensitive to an acute increase in O(2) tension at a biologically critical time point.