Functional comparison of renal Na-K-Cl cotransporters between distant species

Am J Physiol Cell Physiol. 2003 Feb;284(2):C365-70. doi: 10.1152/ajpcell.00262.2002. Epub 2002 Oct 3.


In the shark (sa), two variants of the renal Na-K-Cl cotransporter (saNKCC2A and saNKCC2F) are produced by alternative splicing of the second transmembrane domain (tm(2)). In mammals, these splice variants, as well as a third variant (NKCC2B), are spatially distributed along the thick ascending limb of Henle and exhibit divergent kinetic behaviors. To test whether different tm(2) in saNKCC2 are also associated with different kinetic phenotypes, we examined the ion dependence of (86)Rb influx for shark and rabbit splice variants expressed in Xenopus laevis oocytes. We found that, in both species, A forms have higher cation affinities than F forms. In regard to Cl affinity, however, the A-F difference was more pronounced in rabbit, and the relationship between transport activity and Cl concentration was not always sigmoidal. These results show that the tm(2) of saNKCC2 is, as in rabbit, important for Cl transport, and they suggest that the ability of the distal NKCC2-expressing segment to extract Cl from the luminal fluid differs among species. We have also found that the renal NKCC2 of distant vertebrates share similar affinities for cations. This finding points to the existence of highly conserved residues that mediate the kinetic behavior of the NKCC2 splice variants.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / physiology
  • Amino Acid Sequence / physiology
  • Animals
  • Cations / metabolism
  • Cell Membrane / metabolism*
  • Chlorides / metabolism
  • Dogfish / metabolism*
  • Epithelial Cells / metabolism*
  • Evolution, Molecular
  • Female
  • Kinetics
  • Loop of Henle / metabolism*
  • Oocytes
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / physiology
  • Rabbits
  • Sodium-Potassium-Chloride Symporters / metabolism*
  • Solute Carrier Family 12, Member 1
  • Xenopus laevis


  • Cations
  • Chlorides
  • Protein Isoforms
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 1