An apical-membrane chloride channel in human tracheal epithelium.
An apical-membrane chloride channel in human tracheal epithelium.
复制标题
人气管上皮中的顶膜氯离子通道。
DOI：
10.1126/science.2424085
复制
发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Welsh,MJ
中科院分区：
文献类型：
--
作者：
Welsh,MJ
由于囊性纤维化患者的气道和汗腺导管上皮细胞对氯离子具有不渗透性，因此气道上皮细胞对氯离子转运的机制一直备受关注。降低的氯离子渗透性阻止气道上皮细胞的正常分泌，从而干扰粘膜纤毛清除并导致疾病的发病率和死亡率。由于氯分泌依赖于并受顶端细胞膜中氯电导的调节，因此使用膜片钳技术直接检查人气管上皮原代培养物中的单通道电流。这些细胞含有一个阴离子选择性通道，该通道在无细胞斑块中不具有强烈的电压门控性或受钙调节。该通道也被羧酸的类似物阻断，其降低完整上皮中的顶端氯电导。当连接到细胞上时，通道被异丙肾上腺素激活，尽管也观察到通道自发打开。然而，在某些情况下，只有在从细胞中切除贴片后才能观察到通道。这些结果表明，该通道是负责顶端氯电导在气道上皮细胞。
The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.