Alanine uptake activates hepatocellular chloride channels.
Alanine uptake activates hepatocellular chloride channels.
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丙氨酸摄取激活肝细胞氯离子通道。
DOI：
10.1152/ajpgi.1997.273.4.g849
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Roman,RM
中科院分区：
文献类型：
--
作者：
Lidofsky,SD;Roman,RM
参与氨基酸的回收和代谢转化的细胞响应于氨基酸摄取而经历尺寸的显著增加。由此产生的细胞肿胀的适应性反应被认为包括通过激活体积敏感性离子通道增加膜K+和Cl−渗透性。这一观点主要基于低渗肿胀的实验模型，但很少有哺乳动物细胞在体内经历低渗挑战。在这里，我们已经研究了体积调节反应的细胞肿胀丙氨酸摄取永生化肝细胞的生理模型。丙氨酸诱导的细胞肿胀之后，细胞体积减少，这与膜Cl−电流的增加在时间上相关。这些电流都依赖于丙氨酸浓度和Na+，这表明电流的刺激Na+耦合丙氨酸摄取。Cl−电流是外向整流的，表现出I−> Br−> Cl−的阴离子渗透性顺序，并被Cl−通道阻断剂5-硝基-2-（3-苯丙氨基）苯甲酸抑制，其特征与实验性低渗应激诱发的一类广泛分布的容量敏感性阴离子通道相似。这些研究结果表明，体积敏感性阴离子通道参与氨基酸摄取的适应性反应，并提供了一个新的生理背景下，这样的通道。
Cells involved in the retrieval and metabolic conversion of amino acids undergo significant increases in size in response to amino acid uptake. The resultant adaptive responses to cell swelling are thought to include increases in membrane K+and Cl−permeability through activation of volume-sensitive ion channels. This viewpoint is largely based on experimental models of hypotonic swelling, but few mammalian cells experience hypotonic challenge in vivo. Here we have examined volume regulatory responses in a physiological model of cell-swelling alanine uptake in immortalized hepatocytes. Alanine-induced cell swelling was followed by a decrease in cell volume that was temporally associated with an increase in membrane Cl−currents. These currents were dependent both on alanine concentration and Na+, suggesting that currents were stimulated by Na+-coupled alanine uptake. Cl−currents were outwardly rectifying, exhibited an anion permeability sequence of I−> Br−> Cl−, and were inhibited by the Cl−channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid, features similar to those reported for a widely distributed class of volume-sensitive anion channels evoked by experimental hypotonic stress. These findings suggest that volume-sensitive anion channels participate in adaptive responses to amino acid uptake and provide such channels with a new physiological context.