Effect of electroneutral luminal and basolateral lactate transport on intracellular pH in salamander proximal tubules

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Abstract

We used microelectrodes to examine the effects of organic substrates, particularly lactate (Lac−), on the intracellular pH (pHi) and basolateral membrane potential (Vbl) in isolated, perfused proximal tubules of the tiger salamander. Exposure of the luminal and basolateral membranes to 3.6 mM Lac− caused pHi to increase by ~0.2, opposite to the decrease expected from nonionic diffusion of lactic acid (HLac) into the cell. Addition of Lac− to only the lumen also caused alkalinization, but only if Na+ was present. This alkalinization was not accompanied by immediate Vbl changes, which suggests that it involves luminal, electroneutral Na/Lac cotransport. Addition of Lac" to only the basolateral solution caused pHi to decrease by ~0.08. The initial rate of this acidification was a saturable function of [Lac−], was not affected by removal of Na+, and was reversibly reduced by a-cyano-4-hydroxycinnamate (CHC). Thus, the pHi decrease induced by basolateral Lac− appears to be due to the basolateral entry of H+ and Lac−, mediated by an H/Lac cotransporter (or a Lac-base exchanger). Our data suggest that this transporter is electroneutral and is not present at the luminal membrane. A key question is how the addition of Lac− to the lumen increases pH. We found that inhibition of basolateral H/Lac cotransport by basolateral CHC reduced the initial rate of pHi increase caused by luminal Lac−. On the other hand, luminal CHC had no effect on the luminal Lac−-induced alkalinization. These data suggest that when Lac− is present in the lumen, it enters the cell from the lumen via electroneutral Na/ Lac cotransport and then exits with H+ across the basolateral membrane via electroneutral H/Lac cotransport. The net effect is transepithelial Lac− reabsorption, basolateral acid extrusion, and intracellular alkalinization. © 1987, Rockefeller University Press., All rights reserved.

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Siebens, A. W., & Boron, W. F. (1987). Effect of electroneutral luminal and basolateral lactate transport on intracellular pH in salamander proximal tubules. Journal of General Physiology, 90(6), 799–831. https://doi.org/10.1085/jgp.90.6.799

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