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Abstract：
The paper reviews the evidence for apparent sodium-dependent copper (Cu) uptake across epithelia such as frog skin, fish gills and vertebrate intestine. Potential interactions between Na(+) and Cu during transfer through epithelial cells is rationalized into the major steps of solute transfer: (i) adsorption on to the apical/mucosal membrane, (ii) import in to the cell (iii) intracellular trafficking, and (iv) export from the cell to the blood. Interactions between Na(+) and Cu transport are most likely during steps (i) and (ii). These ions have similar mobilities (lambda) in solution (lambda, Na(+), 50.1; Cu(2+), 53.6 cm(2) Int. ohms(-1) equiv(-1)); consequently, Cu(2+) may compete equally with Na(+) for diffusion to membrane surfaces. We present new data on the Na(+) binding characteristics of the gill surface (gill microenvironment) of rainbow trout. The binding characteristics of Na(+) and Cu(2+) to the external surface of trout gills are similar with saturation of ligands at nanomolar concentrations of solutes. At the mucosal/apical membrane of several epithelia (fish gills, frog skin, vertebrate intestine), there is evidence for both a Cu-specific channel (CTR1 homologues) and Cu leak through epithelial Na(+) channels (ENaC). Cu(2+) slows the amiloride-sensitive short circuit current (I(sc)) in frog skin, suggesting Cu(2+) binding to the amiloride-binding site of ENaC. We present examples of data from the isolated perfused catfish intestine showing that Cu uptake across the whole intestine was reduced by 50% in the presence of 2 mM luminal amiloride, with 75% of the overall inhibition attributed to an amiloride-sensitive region in the middle intestine. Removal of luminal Na(+) produced more variable results, but also reduced Cu uptake in catfish intestine. These data together support Cu(2+) modulation of ENaC, but not competitive entry of Cu(2+) through ENaC. However, in situations where external Na(+) is only a few millimoles (fish gills, frogs in freshwater), Cu(2+) leak through ENaC is possible. CTR1 is a likely route of Cu(2+) entry when external Na(+) is higher (e.g. intestinal epithelia). Interactions between Na(+) and Cu ions during intracellular trafficking or export from the cell are unlikely. However, effects of intracellular chloride on the Cu-ATPase or ENaC indicate that Na(+) might indirectly alter Cu flux. Conversely, Cu ions inhibit basolateral Na(+)K(+)-ATPase and may increase [Na(+)](i).
摘要：
本文回顾了跨上皮（例如青蛙皮肤）明显的钠依赖性铜（Cu）吸收的证据，鱼片和脊椎动物肠。通过上皮细胞转移过程中Na（）和Cu之间的潜在相互作用被合理化为溶质转移的主要步骤：（i）吸附到顶端/粘膜上，(ii)导入细胞(iii)细胞内运输，和(iv)从细胞输出到血液。在步骤(i)和(ii)期间,Na(+)和Cu迁移之间的相互作用是最可能的。这些离子在溶液中具有相似的迁移率（lambda）（lambda，Na(+),50.1;Cu(2+),53.6厘米（2）Int.ohms(-1)equiv(-1));因此,Cu(2+)可以与Na(+)同等地竞争扩散到膜表面。我们提供了有关虹鳟鱼g表面（g微环境）的Na（）结合特性的新数据。Na（）和Cu（2）与鳟鱼g的外表面的结合特性与在溶质的纳摩尔浓度下配体的饱和相似。在几个上皮的粘膜/顶膜（鱼ill，青蛙的皮肤,脊椎动物肠)，有证据表明Cu特异性通道（CTR1同源物）和Cu通过上皮Na（ENaC）通道（ENaC）泄漏。Cu（2+）减缓青蛙皮肤中对阿米洛利敏感的短路电流（I（SC）），提示Cu(2+)与ENaC的阿米洛利结合位点结合。我们提供了来自分离的灌注cat鱼肠道的数据示例，表明在存在2mM腔阿米洛利的情况下，整个肠道的Cu吸收减少了50％，总抑制作用的75％归因于中肠的阿米洛利敏感区域。去除腔内Na（+）产生了更多可变的结果，同时也降低了鲶鱼肠道对铜的吸收。这些数据共同支持ENaC的Cu（2+）调制，但不是通过ENaC竞争性进入Cu(2+)。然而,在外部Na(+)只有几毫摩尔(鱼ill，淡水中的青蛙)，Cu(2+)通过ENaC泄漏是可能的。当外部Na(+)较高时(例如肠上皮),CTR1是Cu(2+)进入的可能途径。在细胞内运输或从细胞输出期间，Na（）和Cu离子之间的相互作用不太可能。然而,细胞内氯化物对Cu-ATPase或ENaC的影响表明Na（）可能间接改变Cu通量。相反，Cu离子抑制基底外侧Na(+)K(+)-ATPase并可增加[Na(+)](i)。
