Ganz M B, Saksa B A
Department of Medicine, Section of Nephrology, Case Western Reserve University, Cleveland, Ohio, USA.
Am J Physiol. 1998 Mar;274(3):F550-5. doi: 10.1152/ajprenal.1998.274.3.F550.
Developmental changes in activity or expression of transporters may account for alterations in cell behavior as the nonpolarized cell matures. We sought to ascertain whether there is a maturational change in each of the major acid-base transporters in the developing mesangial cell (MC), the Na/H exchanger, Na-dependent Cl/HCO3 exchanger, and the Cl/HCO3 exchanger. Intracellular pH (pHi) was determined by the use of the fluorescent pH-sensitive dye, 2',7'-bis(2- carboxyethyl)-5(6)-carboxyfluorescein (BCECF). We assessed transporter activity by studying recovery from an acid load (NH4/NH3) in CO2/HCO3. In adult MCs, Na/H exchanger was responsible for 35.2 +/- 4.3% of steady-state pHi, whereas the Na-dependent Cl/HCO3 exchanger contributed 58.7 +/- 6.1 (n = 14). In term MCs (tMCs), from days 1-3 after birth, the Na/H exchanger contributes 62.9 +/- 7.8% (n = 11, P < 0.001 vs. adult), whereas the Na-dependent Cl/HCO3 exchanger contributes 34.0 +/- 5.7% (n = 12, P < 0.001 vs. adult), to the rate of recovery from an acid load in these cells. However, in tMCs (days 4-6), the Na/H contributes 47.2 +/- 5.9% (n = 8, P < 0.05 vs. adult), whereas the Na-dependent Cl/HCO3 exchanger contributes 48.7 +/- 7.3% (n = 13, P < 0.05 vs. adult), to the rate of recovery. tMCs (days 6-12) yielded transporter activity that was not statistically different than adult MCs (37.8 +/- 4.9 and 54.3 +/- 10.2% for Na/H and Na-dependent Cl/HCO3, respectively). The magnitude of the stimulated response to angiotensin II by Na/H and Na-dependent Cl/HCO3 exchanger in adult and tMCs is unchanged throughout development. The Na/H exchanger appears to play a greater role in pHi homeostasis earlier on in development, and this may reflect developmental needs of the maturing cell.
随着非极化细胞的成熟，转运体活性或表达的发育变化可能导致细胞行为的改变。我们试图确定在发育中的系膜细胞（MC）中，主要的酸碱转运体（钠氢交换体、钠依赖氯/碳酸氢根交换体和氯/碳酸氢根交换体）是否存在成熟变化。细胞内pH值（pHi）通过使用荧光pH敏感染料2',7'-双（2-羧乙基）-5（6）-羧基荧光素（BCECF）来测定。我们通过研究在CO2/碳酸氢根中酸负荷（NH4/NH3）后的恢复情况来评估转运体活性。在成年MC中，钠氢交换体负责35.2±4.3%的稳态pHi，而钠依赖氯/碳酸氢根交换体贡献了58.7±6.1%（n = 14）。在出生后1-3天的足月MC（tMC）中，钠氢交换体贡献62.9±7.8%（n = 11，与成年相比P < 0.001），而钠依赖氯/碳酸氢根交换体贡献34.0±5.7%（n = 12，与成年相比P < 0.001），用于这些细胞中酸负荷后的恢复率。然而，在tMC（4-6天）中，钠氢交换体贡献47.2±5.9%（n = 8，与成年相比P < 0.05），而钠依赖氯/碳酸氢根交换体贡献48.7±7.3%（n = 13，与成年相比P < 0.05），用于恢复率。tMC（6-12天）产生的转运体活性与成年MC无统计学差异（钠氢交换体和钠依赖氯/碳酸氢根交换体分别为37.8±4.9%和54.3±10.2%）。在整个发育过程中，成年和tMC中钠氢交换体和钠依赖氯/碳酸氢根交换体对血管紧张素II刺激反应的幅度没有变化。钠氢交换体在发育早期似乎在pHi稳态中发挥更大作用，这可能反映了成熟细胞的发育需求。
