Functional interaction between bicarbonate transporters and carbonic anhydrase modulates lactate uptake into mouse cardiomyocytes

Jan Peetz, L. Felipe Barros, Alejandro San Martín, Holger M. Becker*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

4 Citas (Scopus)

Resumen

Blood-derived lactate is a precious energy substrate for the heart muscle. Lactate is transported into cardiomyocytes via monocarboxylate transporters (MCTs) together with H+, which couples lactate uptake to cellular pH regulation. In this study, we have investigated how the interplay between different acid/base transporters and carbonic anhydrases (CA), which catalyze the reversible hydration of CO2, modulates the uptake of lactate into isolated mouse cardiomyocytes. Lactate transport was estimated both as lactate-induced acidification and as changes in intracellular lactate levels measured with a newly developed Förster resonance energy transfer (FRET) nanosensor. Recordings of intracellular pH showed an increase in the rate of lactate-induced acidification when CA was inhibited by 6-ethoxy-2-benzothiazolesulfonamide (EZA), while direct measurements of lactate flux demonstrated a decrease in MCT transport activity, when CA was inhibited. The data indicate that catalytic activity of extracellular CA increases lactate uptake and counteracts intracellular lactate-induced acidification. We propose a hypothetical model, in which HCO3 , formed from cell-derived CO2 at the outer surface of the cardiomyocyte plasma membrane by membrane-anchored, extracellular CA, is transported into the cell via Na+/HCO3 cotransport to counteract intracellular acidification, while the remaining H+ stabilizes extracellular pH at the surface of the plasma membrane during MCT activity to enhance lactate influx into cardiomyocytes.

Idioma originalInglés
Páginas (desde-hasta)1469-1480
Número de páginas12
PublicaciónPflugers Archiv European Journal of Physiology
Volumen467
N.º7
DOI
EstadoPublicada - 2015
Publicado de forma externa

Nota bibliográfica

Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.

Áreas temáticas de ASJC Scopus

  • Fisiología
  • Bioquímica clínica
  • Fisiología (médica)

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