Durand J
Institut de Physiologie, Faculté des Sciences, Université de Fribourg.
Arch Int Physiol Biochim. 1988 Sep;96(4):A347-62.
The mucosa that lines the airways is covered with a fluid film forming a hypophase between mucus and cell surface. To study the function of this epithelium aims at describing the mechanisms by which fluid is normally produced. Another goal to be pursued consists in looking for the origin of pathological situations, such as cystic fibrosis, in which the functioning of epithelial cell is altered. The elucidation of transport mechanisms present in the apical and in the basolateral membrane results in a conceptual model that illustrates the asymmetrical functioning of epithelial cells. Recent discoveries enlarge our understanding of membrane transport processes; in particular, a concerted, reciprocal regulation of the activity of both membranes was shown to be exerted via the intracellular composition. The tracheal epithelium absorbs Na+ and secretes Cl-. These two transports are active and electrogenic; their sum corresponds approximately to the short-circuit current measured in vitro. Na+ absorption is sensitive to amiloride from the luminal side and also to ouabain added to the serosal compartment. The process is a primary active transport, analogous to that found in amphibian epithelia or in mammalian colon. Cl- secretion is abolished by furosemide (or bumetanide), by ouabain or by Na+ suppression in the serosal incubation solution. The mechanism is a secondary active transport: Cl- influx across the basolateral membrane is coupled to Na+ (probably through Na+, K+, Cl- symport); energy is dissipated by the Na+-K+-ATPase localised in the basolateral membrane. Thus, Na+ is recirculated across that membrane by the pump activity, which maintains a favorable gradient for influx via the symport. Cl- efflux takes place by diffusion through the luminal membrane. This model applies to other epithelia in which Na+-coupled Cl- secretion was shown to take place. It is confirmed by isotopic fluxes measurements and by electrophysiologic properties of the apical and the basolateral membrane. Various agents are known to influence ion transports. In particular Cl- secretion is stimulated by substances that increase the intracellular concentration of cyclic AMP. At the membrane level, the number of active Cl- channels in the apical membrane is primarily controlled, then the basolateral membrane K+ permeability. Yet, species differences are worth to note: the trachea of the cow is barely sensitive to agents that exert a marked action on dog trachea. The tracheal epithelium is used as an experimental model for studying cystic fibrosis, a disease in which the apical membrane is almost devoid of functional Cl- channels, so that Cl- permeability is quite low.(ABSTRACT TRUNCATED AT 400 WORDS)
气道内衬的黏膜覆盖着一层液膜，在黏液和细胞表面之间形成一个液相层。研究这种上皮组织的功能旨在描述正常情况下液体产生的机制。另一个需要探索的目标是寻找病理状况的根源，比如囊性纤维化，在这种疾病中上皮细胞的功能会发生改变。对顶端膜和基底外侧膜中存在的转运机制的阐明，得出了一个概念模型，该模型阐释了上皮细胞的不对称功能。最近的发现扩展了我们对膜转运过程的理解；特别是，已表明通过细胞内成分对这两种膜的活性进行协同、相互调节。气管上皮细胞吸收Na⁺并分泌Cl⁻。这两种转运都是主动的且是生电的；它们的总和大约相当于体外测量的短路电流。从管腔侧来看，Na⁺吸收对氨氯吡脒敏感，对添加到浆膜腔的哇巴因也敏感。这个过程是一种原发性主动转运，类似于在两栖类上皮或哺乳动物结肠中发现的那种。呋塞米（或布美他尼）、哇巴因或浆膜孵育液中Na⁺的抑制会消除Cl⁻分泌。其机制是继发性主动转运：Cl⁻通过基底外侧膜的内流与Na⁺偶联（可能通过Na⁺、K⁺、Cl⁻同向转运体）；能量通过位于基底外侧膜的Na⁺ - K⁺ - ATP酶消耗。因此，Na⁺通过泵的活性在该膜上再循环，这维持了一个有利于通过同向转运体流入的梯度。Cl⁻通过管腔膜的扩散而外流。这个模型适用于其他已表明存在Na⁺偶联Cl⁻分泌的上皮组织。它通过同位素通量测量以及顶端膜和基底外侧膜的电生理特性得到证实。已知各种因素会影响离子转运。特别是，Cl⁻分泌会受到增加细胞内环磷酸腺苷浓度的物质的刺激。在膜水平上，首先控制顶端膜中活性Cl⁻通道的数量，然后是基底外侧膜的K⁺通透性。然而，物种差异值得注意：牛的气管对那些对狗气管有显著作用的物质几乎不敏感。气管上皮组织被用作研究囊性纤维化的实验模型，在这种疾病中，顶端膜几乎没有功能性Cl⁻通道，因此Cl⁻通透性相当低。（摘要截选至400字）
