A role for sodium-chloride cotransporters in the rapid regulation of ion uptake following acute environmental acidosis: new insights from the zebrafish model

Am J Physiol Cell Physiol. 2016 Dec 1;311(6):C931-C941. doi: 10.1152/ajpcell.00180.2016. Epub 2016 Oct 26.


The effects of acute exposure to acidic water on Na+ and Cl- homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na+ uptake and whole body Na+ content. Nevertheless, the capacity for Na+ uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na+-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na+ enrichment after preexposure to acidic water: H+-ATPase rich (HR) cells, which coexpress the Na+/H+ exchanger isoform 3b (NHE3b), and a non-HR cell population. In fish experiencing Na+-Cl- cotransporter (NCC) knockdown, we observed no Sodium Green accumulation in the latter cell type, suggesting the non-HR cells were NCC cells. Elimination of NHE3b-expressing HR cells did not prevent the increased Na+ uptake following acid exposure. On the other hand, the increased Na+ uptake was abolished when the acidic water was enriched with Na+ and Cl-, but not with Na+ only, indicating that the elevated Na+ uptake after acid exposure was associated with the compensatory regulation of Cl- Further examinations demonstrated that acute acid exposure also reduced whole body Cl- levels and increased the capacity for Cl- uptake. Moreover, knockdown of NCC prevented the increased uptake of both Na+ and Cl- after exposure to acidic water. Together, the results of the present study revealed a novel role of NCC in the compensatory regulation of Na+ and Cl- uptake following acute acidosis.

Keywords: Na+-Cl− cotransporter; Na+/H+ exchanger; acidosis; chloride; ionocyte; sodium; zebrafish.

MeSH terms

  • Acidosis / metabolism*
  • Animals
  • Chlorides / metabolism
  • Ions / metabolism*
  • Protein Isoforms / metabolism
  • Proton-Translocating ATPases / metabolism
  • Sodium / metabolism
  • Sodium Chloride Symporters / metabolism*
  • Sodium-Hydrogen Exchangers / metabolism*
  • Zebrafish / metabolism*
  • Zebrafish Proteins / metabolism*


  • Chlorides
  • Ions
  • Protein Isoforms
  • Sodium Chloride Symporters
  • Sodium-Hydrogen Exchangers
  • Zebrafish Proteins
  • Sodium
  • Proton-Translocating ATPases