Publications

• Stoichiometry of the renal sodium-L-lactate cotransporter.

  Barbarat B., Podevin R.A.

  We re-examined the electrical and stoichiometric properties of the Na+-L-lactate cotransporter using highly purified brush-border membrane vesicles prepared from the whole cortex of rabbit kidney. A valinomycin-induced K+ diffusion potential (interior-negative) stimulated Na+ gradient-dependent L- ... >> More

  We re-examined the electrical and stoichiometric properties of the Na+-L-lactate cotransporter using highly purified brush-border membrane vesicles prepared from the whole cortex of rabbit kidney. A valinomycin-induced K+ diffusion potential (interior-negative) stimulated Na+ gradient-dependent L-lactate uptake. However, this stimulation reflected catalytic rather than energetic activation as an inside-negative membrane potential did not induce net uphill lactate accumulation in the presence of Na+ but in the absence of a Na+ concentration gradient. Additional evidence for electroneutrality of the cotransporter was the finding that, under voltage-clamped conditions, L-lactate flux was a hyperbolic function of extravesicular Na+ concentration with a Hill coefficient (n) of 1.0. Moreover, the plot of V/[Na+]n versus V was linear for n = 1, indicating that one Na+ ion is co-transported with an anionic lactate1-molecule. Finally, addition of L-lactate to vesicles under Na+ equilibrium conditions failed to generate an inside-positive membrane potential as monitored by 3,3'-dipropylthiodicarbocyanine iodide fluorescence quenching, arguing against Na+-L-lactate cotransport by an electrogenic process. Taken together, these data indicate that the luminal Na+-L-lactate co-transporter is electroneutral with a stoichiometry of 1. << Less

  J Biol Chem 263:12190-12193(1988) [PubMed] [EuropePMC]

• Zebrafish Slc5a12 encodes an electroneutral sodium monocarboxylate transporter (SMCTn). A comparison with the electrogenic SMCT (SMCTe/Slc5a8).

  Plata C., Sussman C.R., Sindic A., Liang J.O., Mount D.B., Josephs Z.M., Chang M.-H., Romero M.F.

  We have identified and characterized two different sodium-coupled monocarboxylate cotransporters (SMCT) from zebrafish (Danio rerio), electrogenic (zSMCTe) and electroneutral (zSMCTn). zSMCTn is the 12th member of the zebrafish Slc5 gene family (zSlc5a12). Both zSMCT sequences have approximately 5 ... >> More

  We have identified and characterized two different sodium-coupled monocarboxylate cotransporters (SMCT) from zebrafish (Danio rerio), electrogenic (zSMCTe) and electroneutral (zSMCTn). zSMCTn is the 12th member of the zebrafish Slc5 gene family (zSlc5a12). Both zSMCT sequences have approximately 50% homology to human SLC5A8 (hSMCT). Transport function and kinetics were measured in Xenopus oocytes injected with zSMCT cRNAs by measurement of intracellular Na(+) concentration ([Na(+)](i)) and membrane potential. Both zSMCTs oocytes increased [Na(+)](i) with addition of monocarboxylates (MC) such as lactate, pyruvate, nicotinate, and butyrate. By using two electrode voltage clamp experiments, we measured currents elicited from zSMCTe after MC addition. MC-elicited currents from zSMCTe were similar to hSMCT currents. In contrast, we found no significant MC-elicited current in either zSMCTn or control oocytes. Kinetic data show that zSMCTe has a higher affinity for lactate, nicotinate, and pyruvate (K(m)(L-lactate) = 0.17 +/- 0.02 mM, K(m)(nicotinate) = 0.54 +/-0.12 mM at -150 mV) than zSMCTn (K(m)(L-lactate) = 1.81 +/-0.19 mM, K(m)(nicotinate) = 23.68 +/-4.88 mM). In situ hybridization showed that 1-, 3-, and 5-day-old zebrafish embryos abundantly express both zSMCTs in the brain, eyes, intestine, and kidney. Within the kidney, zSMCTn mRNA is expressed in pronephric tubules, whereas zSMCTe mRNA is more distal in pronephric ducts. zSMCTn is expressed in exocrine pancreas, but zSMCTe is not. Roles for Na(+)-coupled monocarboxylate cotransporters have not been described for the brain or eye. In summary, zSMCTe is the zebrafish SLC5A8 ortholog, and zSMCTn is a novel, electroneutral SMCT (zSlc5a12). Slc5a12 in higher vertebrates is likely responsible for the electroneutral Na(+)/lactate cotransport reported in mammalian and amphibian kidneys. << Less

  J. Biol. Chem. 282:11996-12009(2007) [PubMed] [EuropePMC]

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