Wild type but not Delta F508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes
Wild type but not Delta F508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes
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DOI：
10.1016/0014-5793(96)00079-8
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发表时间：
1996-02-26
期刊：
影响因子：
3.5
通讯作者：
Kunzelmann, K
中科院分区：
文献类型：
--
作者：
Mall, M;Hipper, A;Kunzelmann, K
携带囊性纤维化 (CF) 跨膜电导调节因子 (CFTR) 突变的气道上皮细胞具有增加的 Na+ 电导以及其众所周知的 cAMP 依赖性 Cl- 电导缺陷。目前尚不清楚这种情况的发生，以及是否是由于 CFTR 对上皮 Na+ 电导的控制而导致 CF 患者可能存在缺陷。在本研究中，我们试图通过在爪蟾卵母细胞中过表达各自的 cRNA 来确定 CFTR 与上皮 Na+ 电导之间可能的相互作用。大鼠上皮 Na+ 通道 (rENaC) 和野生型 (wt) CFTR 的所有三个 (α、β、γ) 亚基的表达导致了预期的结果阿米洛利敏感的 Na+ 和 IBMX (1 mmol/l) 分别激活 Cl- 电流，然而，当通过磷酸二酯酶抑制 (IBMX) 激活 wt-CFTR Cl- 电导时，阿米洛利敏感的 Na+ 电导受到抑制。相反，IBMX 在共表达卵母细胞的 Delta F508 和 Na+ 通道中没有这种作用。这些结果表明 wt-CFTR（而非 Delta F508-CFTR）是 cAMP 依赖性的上皮Na+通道的下调剂。这可以解释CF患者气道上皮细胞中观察到的较高Na+电导。
Airway epithelial cells bearing mutations of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) possess an increased Na+ conductance along with their well described defect of cAMP dependent Cl- conductance. Currently it is not clear, holy this occurs, and whether it is due to a CFTR control of epithelial Na+ conductances which might be defective in CF patients, In the present study, we have tried to identify possible interactions between both CFTR and the epithelial Na+ conductance by overexpressing respective cRNAs in Xenopus oocytes, The expression of all three (alpha, beta, gamma) subunits of the rat epithelial Na+ channel (rENaC) and wild type (wt) CFTR resulted in the expected amiloride sensitive Na+ and IBMX (1 mmol/l) activated Cl- currents, respectively, The amiloride sensitive Na+ conductance was, however, inhibited when the wt-CFTR Cl- conductance was activated by phosphodiesterase inhibition (IBMX), In contrast, IBMX had no such effect in Delta F508 and Na+ channels coexpressing oocytes, These results suggest that wt-CFTR, but not Delta F508-CFTR, is a cAMP dependent downregulator of epithelial Na+ channels. This may explain the higher Na+ conductance observed in airway epithelial cells of CF patients.