Chloride/formate exchange with formic acid recycling: a mechanism of active chloride transport across epithelial membranes.

The pathways for transport of Cl- and formate in microvillus membrane vesicles isolated from rabbit renal cortex were evaluated. An outward formate gradient stimulated the uptake of Cl-, and an outward Cl- gradient stimulated the uptake of formate, indicating Cl-/formate exchange. In addition, an inside alkaline pH gradient induced the accumulation of formate, consistent with nonionic diffusion of formic acid. Although an inward Na+ gradient also stimulated uphill formate accumulation, suggesting Na+/formate cotransport, this effect was abolished when ionophores were used to prevent the generation of a transmembrane pH gradient, indicating an indirect coupling of formic acid transport to Na+/H+ exchange. An inside alkaline pH gradient only minimally stimulated the uptake of 82Br-, used as tracer for Cl-, confirming the absence of appreciable Cl-/OH- exchange. However, the same pH gradient in the presence of a physiologic formate concentration (0.2 mM) markedly stimulated 82Br- influx. These data suggest that Cl-/formate exchange with recycling of formic acid by nonionic diffusion is a potential mechanism for active Cl- absorption across the luminal membrane in the proximal tubule and perhaps in other epithelia.