Interaction of H+ with the extracellular and intracellular aspects of hMATE1

Am J Physiol Renal Physiol. 2011 Sep;301(3):F520-8. doi: 10.1152/ajprenal.00075.2011. Epub 2011 May 25.


Human multidrug and toxin extrusion 1 (hMATE1, SLC47A1) is a major candidate for being the molecular identity of organic cation/proton (OC/H(+)) exchange activity in the luminal membrane of renal proximal tubules. Although physiological function of hMATE1 supports luminal OC efflux, the kinetics of hMATE1-mediated OC transport have typically been characterized through measurement of uptake, i.e., the interaction between outward-facing hMATE1 and OCs. To examine kinetics of hMATE1-mediated transport in a more physiologically relevant direction, i.e., an interaction between inward-facing hMATE1 and cytoplasmic substrates, we measured the time course of hMATE1-mediated efflux of the prototypic MATE1 substrate, [(3)H]1-methyl-4-phenylpyridinium, under a variety of intra- and extracellular pH conditions, from Chinese hamster ovary cells that stably expressed the transporter. In this study, we showed that an IC(50)/K(i) for interaction between extracellular H(+) and outward-facing hMATE1 determined from conventional uptake experiments [12.9 ± 1.23 nM (pH 7.89); n = 9] and from the efflux protocol [14.7 ± 3.45 nM (pH 7.83); n = 3] was not significantly different (P = 0.6). Furthermore, kinetics of interaction between intracellular H(+) and inward-facing hMATE1 determined using the efflux protocol revealed an IC(50) for H(+) of 11.5 nM (pH 7.91), consistent with symmetrical interactions of H(+) with the inward-facing and outward-facing aspects of hMATE1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / physiology
  • CHO Cells
  • Cations / metabolism
  • Cricetinae
  • Cricetulus
  • Cytoplasm / metabolism*
  • Extracellular Matrix / metabolism*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Models, Animal
  • Organic Cation Transport Proteins / metabolism*
  • Ovary / cytology
  • Ovary / metabolism
  • Protons*
  • Transfection


  • Cations
  • Organic Cation Transport Proteins
  • Protons
  • SLC47A1 protein, human