Flynn Andrea N, Itani Omar A, Moninger Thomas O, Welsh Michael J
Howard Hughes Medical Institute, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3591-6. doi: 10.1073/pnas.0813393106. Epub 2009 Feb 10.
Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La(3+) movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na(+) conductance, with a smaller increase in Cl(-) conductance. The increase was mediated by histamine H(1) receptors and depended on an increase in intracellular Ca(2+) concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport.
电解质通过气道上皮细胞以及在气道上皮细胞之间的转运控制着其表面液体的量和成分。许多研究表明气道上皮细胞的跨细胞离子转运存在急性调节。然而，无论是在气道上皮还是其他上皮中，通过紧密连接的离子转运是否也能被急性调节，目前还知之甚少。为了研究细胞旁途径，我们使用了分化的人气道上皮细胞原代培养物，评估了紧密连接蛋白（细胞旁通透性的主要决定因素）的表达，并测量了跨上皮电特性、离子通量和镧离子（La(3+)）的移动。与许多其他组织一样，气道上皮表达多种紧密连接蛋白。此外，上皮中的不同细胞类型表达相同模式的紧密连接蛋白。为了评估紧密连接调节，我们检测了对组胺（一种气道功能的急性调节因子）的反应。组胺刺激细胞旁钠离子电导迅速短暂增加，氯离子电导增加较小。这种增加是由组胺H(1)受体介导的，并且依赖于细胞内钙离子浓度的增加。这些结果表明通过细胞旁途径的离子流动可以被急性调节。这种调节可能有助于将反向离子的被动流动与主动跨细胞转运偶联起来，从而控制净跨上皮盐和水的转运。
