Revisiting voltage-coupled H+ secretion in the collecting duct

Niklas Ayasse, Peder Berg, Mads V Sørensen, Samuel L Svendsen, Alan M Weinstein, Jens Leipziger

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Abstract

Experimental studies have shown that V-type ATPase-driven H+ secretion is dependent on transepithelial voltage. On this basis, the “voltage hypothesis” of urinary acidification by the collecting duct was derived. Accordingly, it has been supposed that the lumen-negative potential created by the reabsorption of Na+ via the epithelial Na+ channel (ENaC) enhances electrogenic H+ secretion via V-type H+-ATPase. This concept continues to be widely used to explain acid/base disorders. Importantly, however, a solid proof of principle for the voltage hypothesis in physiologically relevant situations has not been reached. Rather, it has been challenged by recent in vivo functional studies. In this review, we outline the arguments and experimental observations explaining why voltage-coupled H+ secretion in the collecting duct often appears poorly applicable for rationalizing changes in H+ secretion as a function of more or less ENaC function in the collecting duct.

Original languageEnglish
JournalAmerican journal of physiology. Renal physiology
Volume327
Issue6
Pages (from-to)F931-F945
Number of pages15
ISSN1931-857X
DOIs
Publication statusPublished - Dec 2024

Keywords

  • ENaC
  • acid/base handling
  • collecting duct
  • diuretics
  • transepithelial voltage

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