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Facilitated Lactate Transport by MCT1 when Coexpressed with the Sodium Bicarbonate Cotransporter (NBC) in Xenopus Oocytes

Holger M. Becker ^*, Stefan Bröer  and Joachim W. Deitmer ^*

^* Abteilung für Zoologie, FB Biologie, Universität Kaiserslautern, D-67653 Kaiserslautern, Germany; and School of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra, ACT 0200, Australia

Correspondence: Address reprint requests to J. W. Deitmer, Abteilung für Zoologie, FB Biologie, Universität Kaiserslautern, Postfach 3049, D-67653 Kaiserslautern, Germany. Tel.: +49-631-205-2877; Fax: +49-631-205-3515; E-mail: deitmer{at}rhrk.uni-kl.de.

Monocarboxylate transporters (MCT) and sodium-bicarbonate cotransporters (NBC) transport acid/base equivalents and coexist in many epithelial and glial cells. In nervous systems, the electroneutral MCT1 isoform cotransports lactate and other monocarboxylates with H⁺, and is believed to be involved in the shuttling of energy-rich substrates between astrocytes and neurons. The NBC cotransports bicarbonate with sodium and generates a membrane current. We have expressed these transporter proteins, cloned from rat brain (MCT1) and human kidney (NBC), alone and together, by injecting the cRNA into oocytes of the frog Xenopus laevis, and measured intracellular pH changes and membrane currents under voltage-clamp with intracellular microelectrodes, and radiolabeled lactate uptake into the oocytes. We determined the cytosolic buffer capacity, the H⁺ and lactate fluxes as induced by 3 and 10 mM lactate in oocytes expressing MCT1 and/or NBC, and in water-injected oocytes, in salines buffered with 5 mM HEPES alone or with 5% CO₂/10 mM HCO₃^- (pH 7.0). In MCT1 + NBC- but not in MCT1- or NBC-expressing oocytes, lactate activated a Na⁺- and HCO₃^--dependent membrane current, indicating that lactate/H⁺ cotransport via MCT1, due to the induced pH change, stimulates NBC activity. Lactate/H⁺ cotransport by MCT1 was increased about twofold when MCT1 was expressed together with NBC. Our results suggest that the facilitation of MCT1 transport activity is mainly due to the increase in apparent buffer capacity contributed by the NBC, and thereby suppresses the build-up of intracellular H⁺ during the influx of lactate/H⁺, which would reduce MCT1 activity. Hence these membrane transporters functionally cooperate and are able to increase ion/metabolite transport activity.

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