Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats.
Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats.
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高氧大鼠肺泡 II 型细胞中钠通道的表达和活性增加。
DOI：
10.1073/pnas.92.18.8418
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发表时间：
1995
影响因子：
11.1
通讯作者：
Matalon,S
中科院分区：
文献类型：
--
作者：
Yue,G;Russell,WJ;Benos,DJ;Jackson,RM;Olman,MA;Matalon,S
我们研究了与高氧(85%O2暴露7天，然后100%O2暴露4天)大鼠肺泡上皮钠转运增加有关的细胞和分子事件。提取肺泡II型(ATII)细胞的RNA，并用大鼠结肠上皮钠通道亚基(αrENaC)的一个亚单位(αrENaC)的cDNA进行检测。从85%O2暴露7天的大鼠分离的ATII细胞RNA中，αrENaC mRNA(3.7kb转录本)增加了3倍，随后100%O2暴露4天后增加了6倍。原位杂交显示，高氧大鼠呼吸道和肺泡上皮细胞中αrENaC mRNA转录产物表达增加。高氧大鼠ATII细胞经抗肾钠通道蛋白多克隆抗体免疫染色后，细胞质膜和细胞质中的免疫原性蛋白含量均显著增加。在全细胞模式下，高氧大鼠的ATII细胞显示阿米洛利和5-(N-乙基-N-异丙基)-2‘，4’-阿米洛利(EIPA)敏感电流，这两种电流比呼吸空气的大鼠高100%。单通道钠电流(平均电导为25ps)在ATII细胞中可见，无论是在内向外模式还是在细胞附着模式下都是如此。在暴露于高氧期间，这些通道的数量和开放概率显著增加。暴露于亚致死性高氧可上调ATII细胞αrENaC mRNA和钠通道的功能表达。
We investigated the cellular and molecular events associated with the increase in sodium transport across the alveolar epithelium of rats exposed to hyperoxia (85% O2 for 7 days followed by 100% O2 for 4 days). Alveolar type II (ATII) cell RNA was isolated and probed with a cDNA for one of the rat colonic epithelial sodium channel subunits (alpha rENaC). The alpha rENaC mRNA (3.7-kb transcript) increased 3-fold in ATII cell RNA isolated from rats exposed to 85% O2 for 7 days and 6-fold after 4 days of subsequent exposure to 100% O2. In situ hybridization revealed increased expression of alpha rENaC mRNA transcripts in both airway and alveolar epithelial cells of hyperoxic rats. When immunostained with a polyclonal antibody to kidney sodium channel protein, ATII cells from hyperoxic rats exhibited a significant increase in the amount of immunogenic protein present in both the plasma membrane and the cytoplasm. When patched in the whole-cell mode, ATII cells from hyperoxic rats exhibited amiloride and 5-(N-ethyl-N-isopropyl)-2',4'-amiloride (EIPA)-sensitive currents that were 100% higher compared with those obtained from air-breathing rats. Single-channel sodium currents (mean conductance of 25 pS) were seen in ATII cells patched in both the inside-out and cell-attached modes. The number and open probability of these channels increased significantly during exposure to hyperoxia. Exposure to sublethal hyperoxia up-regulated both alpha rENaC mRNA and the functional expression of sodium channels in ATII cells.