CO_2 gas transporter in plasma membrane which is involved in gas exchange

O_2和CO_2气体通过质膜的输送对肺泡空间和血流之间维持正常呼吸至关重要。然而，膜气输运机理尚未确定。在我们的初步研究中，我们发现肺泡I型上皮细胞的质膜CO_2气体通透性异常高，提示细胞中存在CO_2气体转运体。因此，我们首先研究了细胞高CO_2气体渗透性的机制。原代培养的大鼠肺泡II型细胞可自发分化为i型样细胞。我们发现水通道蛋白-5 （aquaporin-5, AQP5）的表达水平在该培养中显著升高。结果表明，AQP5在爪蟾卵母细胞中的表达显著提高了其膜的CO_2透性。AQP5突变体在其序列中缺少组氨酸或半胱氨酸残基，没有增加CO_2气体渗透性，说明这些氨基酸的重要性。我们还检测了AQP5在肺泡上皮细胞中的转录调控，发现Sp1转录因子正调控AQP5表达，Sp3转录因子负调控AQP5表达。此外，我们发现维甲酸通过激活Sp1增加AQP5的表达。最后，我们发现一氧化氮通过s -硝基化抑制AQP5活性。这些发现有助于研究肺泡-血液屏障气体交换的生理调节。

O_2 and CO_2 gas transport through plasma membrane is important to maintain normal respiration between alveolar space and blood flow. However, the mechanism of membrane gas transport has not been established. In our preliminary studies, we have found the plasma membrane CO_2 gas permeability of alveolar type I epithelial cell was unusually high, suggesting the cell has CO_2 gas transporter. Therefore, we first examined the mechanism that is involved in high CO_2 gas permeability of the cells. Primary cultured rat alveolar type II cells spontaneously differentiated into type I-like cells. We found the expression level of aquaporin-5 (AQP5) was considerably increased in this culture. Then we found that AQP5 expression in Xenopus oocytes significantly increased membrane CO_2 gas permeability. AQP5 mutants, that lack histidine or cysteine residues in its sequence, did not increased CO_2 gas permeability, suggesting the importance of these amino acids. We also examined the transcriptional regulation of AQP5 in alveolar epithelial cells, and found that Sp1 transcription factor positively and Sp3 negatively regulate AQP5 expression. In addition, we have found that retinoic acid increased AQP5 expression through the activation of Sp1. Finally, we found that nitric oxide inhibited AQP5 activity through S-nitrisylation. These findings are useful to consider the physiological regulation of gas exchange at alveolar-blood barrier.