Internal pH-sensitive site couples Cl-(-)HCO3- exchange to Na+-H+ antiport in lymphocytes

Abstract

Parallel exchange of Na+-H+ and Cl-(-)HCO3- is thought to be central to the translocation of electrolytes and water during cell volume regulation and in transepithelial transport. Coupling between these transporters is thought to be indirect, through changes in the concentration of HCO3-, which result from alterations in cytosolic pH (pHi). The possibility of a more direct, HCO3-(-)independent interaction between Cl-(-)HCO3- exchange and the Na+-H+ antiport was studied in rat thymic lymphocytes. Measurements of radioactive Cl- flux and of HCO3-(-)dependent pHi changes demonstrated the presence of a Na+-independent, 4,4'diisothiocyanostilbene-2,2'-disulfonic acid-sensitive Cl-(-)HCO3- exchanger. At constant external pH, the rate of Cl-(-)HCO3- exchange was markedly accelerated by increasing pHi between 7.0 and 7.4. This activation was not related to variations in the concentration of HCO3- and is likely caused by a direct effect of intracellular H+ (OH-) on the exchanger. Osmotic shrinking of the cells induced a cytoplasmic alkalinization, due to activation of the Na+-H+ antiport. Concomitantly, the rate of anion exchange also increased. The stimulation of Cl-(-)HCO3- exchange was eliminated when the alkalinization caused by Na+-H+ exchange was precluded. These observations suggest that the exquisite pHi sensitivity of the Cl-(-)HCO3- exchange system provides a mechanism whereby the rates of cation and anion transport are closely coupled.

Leucocyte Na+/H+ antiport activity in Type 1 (insulin-dependent) diabetic patients with nephropathy

“…However, the changes in resting intracellular pH in vivo may be corrected by increased Cl-/HCO3-exchange [24]. The net result could be intracellular overload with both Na § and Cl-.…”

Regulation of Intracellular pH in Single Rat Cortical Neurons in vitro: A Microspectrofluorometric Study

“…J Cereb Blood Flow Metab, Vol, 13, No, 5, 1993 Regulation of an alkaline transient An electroneutral anion transport mechanism, passively transporting CI-in exchange for HC03 -, has been extensively studied in erythrocytes but as also been identified in many other mammalian cells, including cultured rat astrocytes (Cabantchik et al, 1978;Reinertsen et al, 1988;Mason et al, 1989;Mellergard et al, 1993). This exchanger is consid ered as a separate HC03 -transport mechanism, inhibited by stilbene derivatives.…”

In situ detection of AE2 anion-exchanger mRNA in the human liver

“…AE proteins seem to be involved in intracellular pH and cell-volume regulation, as well as transepithelial acid/base transport Mason et al 1989;Jennings 1992;Alper 1994). These proteins are encoded by a family of genes, three of which (AE1, AE2, and AE3) are well characterized (reviewed by Kopito 1990;Alper 1994).…”