Hwang T C, Guggino S E, Guggino W B
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5706-9. doi: 10.1073/pnas.87.15.5706.
The effect of fatty acids on Cl- channels and transepithelial Cl- secretion is investigated. Patch-clamp experiments show that arachidonic acid blocks Cl- channels in a dose-dependent manner. Kinetic analysis shows that the mean open time is decreased 10-fold with 25 microM arachidonic acid. There is a linear relationship between the reciprocal of mean open time and blocker concentration within the range of 1 to 25 microM. The reciprocal of mean blocked time does not change with arachidonic acid concentration. Other cis unsaturated fatty acids, including oleic, linoleic, and ricinoleic acids, demonstrate similar blocks. Trans unsaturated acids such as elaidic acid and saturated fatty acids, including stearic, palmitic, and myristic acids, do not inhibit the channel at 20 microM. Ricinoleic acid decreases short circuit current in T84 cells, a colonic carcinoma cell line that secretes Cl-. Our results suggest that the direct effect of arachidonic and other fatty acids on Cl- secretion is to block Cl- channel current.
研究了脂肪酸对氯离子通道和跨上皮氯离子分泌的影响。膜片钳实验表明，花生四烯酸以剂量依赖方式阻断氯离子通道。动力学分析显示，25微摩尔花生四烯酸可使平均开放时间缩短10倍。在1至25微摩尔范围内，平均开放时间的倒数与阻滞剂浓度之间存在线性关系。平均阻断时间的倒数不随花生四烯酸浓度变化。其他顺式不饱和脂肪酸，包括油酸、亚油酸和蓖麻油酸，也表现出类似的阻断作用。反式不饱和酸如反油酸以及饱和脂肪酸，包括硬脂酸、棕榈酸和肉豆蔻酸，在20微摩尔时不抑制该通道。蓖麻油酸可降低T84细胞（一种分泌氯离子的结肠癌细胞系）的短路电流。我们的结果表明，花生四烯酸和其他脂肪酸对氯离子分泌的直接作用是阻断氯离子通道电流。
