More actors in ammonia absorption by the thick ascending limb

Am J Physiol Renal Physiol. 2012 Feb 1;302(3):F293-7. doi: 10.1152/ajprenal.00307.2011. Epub 2011 Nov 16.


This review will briefly summarize current knowledge on the basolateral ammonia transport mechanisms in the thick ascending limb (TAL) of the loop of Henle. This segment transports ammonia against a concentration gradient and is responsible for the accumulation of ammonia in the medullary interstitium, which, in turn, favors ammonia secretion across the collecting duct. Experimental data indicate that the sodium/hydrogen ion exchanger isoform 4 (NHE4; Scl9a4) is a sodium/ammonia exchanger and plays a major role in this process. Disruption of murine NHE4 leads to metabolic acidosis with inappropriate urinary ammonia excretion and decreases the ability of the TAL to absorb ammonia and to build the corticopapillary ammonia gradient. However, NHE4 does not account for the entirety of ammonia absorption by the TAL, indicating that, at least, one more transporter is involved.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acidosis / metabolism*
  • Ammonia / metabolism*
  • Animals
  • Biological Transport / physiology
  • Humans
  • Kidney Cortex / metabolism*
  • Loop of Henle / metabolism*
  • Mice
  • Sodium-Hydrogen Exchangers / metabolism*


  • Slc9a4 protein, mouse
  • Sodium-Hydrogen Exchangers
  • Ammonia