URINARY PROTEASES DEGRADE EPITHELIAL SODIUM-CHANNELS
URINARY PROTEASES DEGRADE EPITHELIAL SODIUM-CHANNELS
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DOI：
10.1007/bf01872741
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发表时间：
1991-05-01
影响因子：
2.4
通讯作者：
CLAUSEN, C
中科院分区：
文献类型：
--
作者：
LEWIS, SA;CLAUSEN, C
哺乳动物膀胱上皮通过细胞质小泡的插入和退出来适应体积变化。 两个顶端膜（这是完全由融合的囊泡）和细胞质囊泡含有三种类型的离子电导，阿米洛利敏感，另一个阳离子选择性电导和第三个阳离子电导，似乎顶端膜和粘膜溶液之间的分区。 顶端膜（已暴露于尿液在体内）的运输特性不同的细胞质囊泡具有较低密度的阿米洛利敏感的通道和可变水平的泄漏电导。 先前表明，腺激肽释放酶能够将上皮钠通道水解成渗漏电导，并且该渗漏电导进一步降解成在顶膜和粘膜溶液之间分配的通道。 本报告研究了激肽释放酶是否是唯一能够改变顶膜离子渗透性的尿液成分，或者其他蛋白酶或离子条件是否也不可逆转地改变顶膜渗透性。粘膜pH值、尿素浓度、钙浓度或渗透压的改变并不会不可逆转地影响顶膜离子电导。 然而，尿激酶和纤溶酶（都是哺乳动物尿液中发现的丝氨酸蛋白酶）被发现会导致阿米洛利敏感电流的不可逆损失，泄漏电流的可变变化以及出现第三个电导，这是不稳定的顶端膜，并出现顶端膜和粘膜溶液之间的分区。 阿米洛利保护阿米洛利敏感的电导水解，但不保护泄漏途径。 这两个通道都不受钠的保护。 波动分析表明，阿米洛利敏感电流的损失是由于钠通道密度的下降，而不是单通道电流的变化。 假设一个简单的模型的顺序退化，单通道电流和电导的泄漏通道和不稳定的泄漏通道的估计。
The mammalian urinary bladder epithelium accommodates volume changes by the insertion and withdrawal of cytoplasmic vesicles. Both apical membrane (which is entirely composed of fused vesicles) and the cytoplasmic vesicles contain three types of ionic conductances, one amiloride sensitive, another a cation-selective conductance and the third a cation conductance which seems to partition between the apical membrane and the mucosal solution. The transport properties of the apical membrane (which has been exposed to urine in vivo) differ from the cytoplasmic vesicles by possessing a lower density of amiloride-sensitive channels and a variable level of leak conductance. It was previously shown that glandular kallikrein was able to hydrolyze epithelial sodium channels into the leak conductance and that this leak conductance was further degraded into a channel which partitioned between the apical membrane and the mucosal solution. This report investigates whether kallikrein is the only urinary constituent capable of altering the apical membrane ionic permeability or whether other proteases or ionic conditions also irreversible modify apical membrane permeability.Alterations of mucosal pH, urea concentrations, calcium concentrations or osmolarity did not irreversible affect the apical membrane ionic conductances. However, urokinase and plasmin (both serine proteases found in mammalian urine) were found to cause an irreversible loss of amiloride-sensitive current, a variable change in the leak current as well as the appearance of a third conductance which was unstable in the apical membrane and appears to partition between the apical membrane and the mucosal solution. Amiloride protects the amiloride-sensitive conductance from hydrolysis but does not protect the leak pathway. Neither channel is protected by sodium. Fluctuation analysis demonstrated that the loss of amiloride-sensitive current was due to a decrease in the sodium-channel density and not a change in the single-channel current. Assuming a simple model of sequential degradation, estimates of single-channel currents and conductances for both the leak channel and unstable leak channel are determined.