title: Role of monocarboxylate transport in the regulation of intracellular pH of renal proximal tubule cells.
abstract: Traditional models of acid-base transport and intracellular pH (pHi) regulation in the renal proximal tubule have been based on the existence of a Na+/H+ exchanger at the luminal membrane and a simple HCO3- conductance at the basolateral membrane. Our recent work, in which we used pH-sensitive microelectrodes or dyes to monitor pHi in isolated renal tubules perfused in the nominal absence of HCO3-, has demonstrated the existence of a novel mechanism of acid extrusion in amphibian and mammalian proximal tubule cells. The salamander proximal tubule, for example, possesses an electroneutral Na+ monocarboxylate (Na+-X-) co-transporter, but only at the luminal membrane. It also possesses an electroneutral H+-X- co-transporter, but only at the blood side or basolateral membrane. In the presence of lactate, the luminal Na+-lactate co-transporter mediates a net influx of lactate, driven by the Na+ gradient. The cell-to-blood lactate gradient, in turn, drives the coupled efflux of H+ and lactate across the basolateral membrane. The net effect is the reabsorption of lactate, the luminal uptake of Na+ and the basolateral extrusion of H+. Acid extrusion mediated by this monocarboxylate system in the salamander is comparable in magnitude to that mediated by the Na+/H+ exchanger. In the S3 segment of the rabbit proximal tubule, a similar monocarboxylate system (studied with acetate instead of lactate) extrudes acetate at twice the rate of the Na+/H+ exchanger. Thus, monocarboxylate transport, at least in the nominal absence of HCO3-, can have a major impact on pHi regulation.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: W F
authors.initials: WF
authors.lastname: Boron
authors.forename: A W
authors.initials: AW
authors.lastname: Siebens
authors.forename: N L
authors.initials: NL
authors.lastname: Nakhoul
mesh_terms: D000085:Acetates / Q000378:metabolism; D000136:Acid-Base Equilibrium; D000557:Ambystoma; D000818:Animals; D001692:Biological Transport; D002264:Carboxylic Acids / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D011817:Rabbits
chemical_list: D000085:Acetates; D002264:Carboxylic Acids; D007773:Lactates; D019344:Lactic Acid