Strazzabosco M, Mennone A, Boyer J L
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
J Clin Invest. 1991 May;87(5):1503-12. doi: 10.1172/JCI115160.
To evaluate ion transport mechanisms in bile duct epithelium (BDE), BDE cells were isolated from bile duct-ligated rats. After short-term culture pHi was measured with a single cell microfluorimetric set-up using the fluorescent pHi indicator BCECF, and calibrated with nigericin in high K+ concentration buffer. Major contaminants were identified using vital markers. In HCO3(-)-free media, baseline pHi (7.03 +/- 0.12) decreased by 0.45 +/- 0.18 pH units after Na+ removal and by 0.12 +/- .04 after amiloride administration (1 mM). After acid loading (20 mM NH4Cl) pHi recovery was inhibited by both Na+ removal and amiloride (JH+ = 0.74 +/- 1.1, and JH+ = 2.28 +/- 0.8, respectively, vs. 5.47 +/- 1.97 and 5.97 +/- 1.76 mM/min, in controls, respectively). In HCO3- containing media baseline pHi was higher (7.16 +/- 0.1, n = 36, P less than 0.05) and was decreased by Na+ substitution but not by amiloride. Na+ removal inhibited pHi recovery after an intracellular acid load (0.27 +/- 0.26, vs. 7.7 +/- 4.1 mM/min, in controls), whereas amiloride reduced JH+ only by 27%. pH recovery was inhibited by DIDS (0.5-1 mM), but not by Cl- depletion. Finally, acute Cl- removal increased pHi by 0.18 pH units in the absence but not presence of DIDS. These data indicate that BDE cells possess mechanisms for Na+/H+ exchange, Na+:HCO3- symport and Cl-/HCO3 exchange. Therefore BDE may be capable of transepithelial H+/HCO3- transport.
为评估胆管上皮(BDE)中的离子转运机制,从胆管结扎的大鼠中分离出BDE细胞。短期培养后,使用荧光pH指示剂BCECF的单细胞微荧光测定装置测量细胞内pH(pHi),并在高钾浓度缓冲液中用尼日利亚菌素进行校准。使用活体标记物鉴定主要污染物。在无HCO3(-)的培养基中,去除Na+后基线pHi(7.03±0.12)降低了0.45±0.18个pH单位,给予氨氯吡咪(1 mM)后降低了0.12±0.04。酸负荷(20 mM NH4Cl)后,去除Na+和氨氯吡咪均抑制了pHi恢复(JH+分别为0.74±1.1和2.28±0.8,而对照组分别为5.47±1.97和5.97±1.76 mM/min)。在含HCO3-的培养基中,基线pHi较高(7.16±0.1,n = 36,P<0.05),经Na+替代后降低,但氨氯吡咪未使其降低。去除Na+抑制了细胞内酸负荷后的pHi恢复(0.27±0.26,而对照组为7.7±4.1 mM/min),而氨氯吡咪仅使JH+降低27%。DIDS(0.5 - 1 mM)抑制了pH恢复,但Cl-耗竭未抑制。最后,在不存在但存在DIDS的情况下,急性去除Cl-使pHi升高0.18个pH单位。这些数据表明BDE细胞具有Na+/H+交换、Na+:HCO3-共转运和Cl-/HCO3交换机制。因此,BDE可能能够进行跨上皮H+/HCO3-转运。