Development of pH regulatory transport in glomerular mesangial cells

Abstract

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/HCO3exchanger 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 pHihomeostasis earlier on in development, and this may reflect developmental needs of the maturing cell.