Kokko K E, Matsumoto P S, Zhang Z R, Ling B N, Eaton D C
Emory University School of Medicine, Department of Physiology, Atlanta, Georgia, USA.
Am J Physiol. 1997 Aug;273(2 Pt 1):C548-57. doi: 10.1152/ajpcell.1997.273.2.C548.
In A6 distal nephron cells, short-circuit current (Isc) was increased by basolateral exposure to prostaglandin E2 (PGE2; peak response at 1 microM). The effect was only partially abolished by either apical amiloride, an Na+ channel blocker, or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), a Cl- channel blocker. In apical cell-attached patches, we observed a 7-pS Cl- channel with a linear current-voltage relationship, a reversal potential near resting membrane potential, and open probability > 0.5. The channel was blocked by diphenylamine-2-carboxylate, glibenclamide, and NPPB but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The frequency of observed Cl- channel activity increased 7-fold with 10-min exposure to PGE2 and 3.7-fold with longer (10-50 min) exposure to PGE2. The PGE2-induced increase in Cl- channel activity was due primarily to an increase in the number of functional channels. The following conclusions were made: 1) activation of apical, 7-pS Cl- channels in A6 cells accounts for the PGE2-induced increase in the amiloride-insensitive Isc, and 2) 7-pS Cl- channel activation was mediated via an increase in channel density without substantial effects on channel kinetics.
在A6远曲小管细胞中，通过将基底外侧暴露于前列腺素E2（PGE2；1 microM时达到峰值反应）可使短路电流（Isc）增加。顶端应用钠通道阻滞剂氨氯地平或氯通道阻滞剂5-硝基-2-（3-苯丙基氨基）苯甲酸（NPPB）只能部分消除该效应。在顶端细胞贴附式膜片中，我们观察到一个7-pS的氯通道，其电流-电压关系呈线性，反转电位接近静息膜电位，开放概率>0.5。该通道被二苯胺-2-羧酸盐、格列本脲和NPPB阻断，但不被4,4'-二异硫氰酸芪-2,2'-二磺酸阻断。暴露于PGE2 10分钟时，观察到的氯通道活性频率增加了7倍，暴露于PGE2更长时间（10 - 50分钟）时增加了3.7倍。PGE2诱导的氯通道活性增加主要是由于功能性通道数量增加。得出以下结论：1）A6细胞顶端7-pS氯通道的激活导致了PGE2诱导的对氨氯地平不敏感的Isc增加，2）7-pS氯通道的激活是通过通道密度增加介导的，对通道动力学没有实质性影响。
