Analysis of an electrostatic mechanism for ΔpH dependent gating of the voltage-gated proton channel, HV1, supports a contribution of protons to gating charge

Biochim Biophys Acta Bioenerg. 2021 Nov 1;1862(11):148480. doi: 10.1016/j.bbabio.2021.148480. Epub 2021 Aug 5.


Voltage-gated proton channels (HV1) resemble the voltage-sensing domain of other voltage-gated ion channels, but differ in containing the conduction pathway. Essential to the functions of HV1 channels in many cells and species is a unique feature called ΔpH dependent gating. The pH on both sides of the membrane strictly regulates the voltage range of channel opening, generally resulting in exclusively outward proton current. Two types of mechanisms could produce ΔpH dependent gating. The "countercharge" mechanism proposes that protons destabilize salt bridges between amino acids in the protein that stabilize specific gating configurations (closed or open). An "electrostatic" mechanism proposes that protons bound to the channel alter the electrical field sensed by the protein. Obligatory proton binding within the membrane electrical field would contribute to measured gating charge. Estimations on the basis of the electrostatic model explain ΔpH dependent gating, but quantitative modeling requires calculations of the electric field inside the protein which, in turn, requires knowledge of its structure. We conclude that both mechanisms operate and contribute to ΔpH dependent gating of HV1.

Keywords: HVCN1; Ion channels; Voltage-dependent gating; Voltage-sensing.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Electromagnetic Fields
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Ion Channel Gating
  • Ion Channels / metabolism*
  • Models, Biological
  • Proton-Motive Force
  • Protons
  • Static Electricity


  • Ion Channels
  • Protons