pH regulation and beyond: unanticipated functions for the voltage-gated proton channel, HVCN1

Trends Cell Biol. 2011 Jan;21(1):20-8. doi: 10.1016/j.tcb.2010.09.006. Epub 2010 Oct 18.


Electrophysiological studies have implicated voltage-gated proton channels in several specific cellular contexts. In neutrophils, they mediate charge compensation that is associated with the oxidative burst of phagocytosis. Molecular characterization of the hydrogen voltage-gated channel 1 (HVCN1) has enabled identification of unanticipated and diverse functions: HVCN1 not only modulates signaling from the B-cell receptor following B-cell activation and histamine release from basophils, but also mediates pH-dependent activation of spermatozoa, as well as acid secretion by tracheal epithelium. The importance of HVCN1 in pH regulation during phagocytosis was established by surprising evidence that indicated its first-responder role. In this review, we discuss recent findings from a functional perspective, and the potential of HVCN1 as a therapeutic target for autoimmune and other diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Basophils
  • Humans
  • Hydrogen-Ion Concentration
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Male
  • Phagocytosis
  • Receptors, Antigen, B-Cell
  • Signal Transduction
  • Spermatozoa / metabolism


  • HVCN1 protein, human
  • Ion Channels
  • Receptors, Antigen, B-Cell