External barium affects the gating of KCNQ1 potassium channels and produces a pore block via two discrete sites

Gilad Gibor, Daniel Yakubovich, Asher Peretz, Bernard Attali

Research output: Contribution to journalArticlepeer-review

Abstract

The pore properties and the reciprocal interactions between permeant ions and the gating of KCNQ channels are poorly understood. Here we used external barium to investigate the permeation characteristics of homomeric KGNQ1 channels. We assessed the Ba2+ binding kinetics and the concentration and voltage dependence of Ba2+ steady-state block. Our results indicate that extracellular Ba2+ exerts a series of complex effects, including a voltage-dependent pore blockade as well as unique gating alterations. External barium interacts with the permeation pathway of KCNQ1 at two discrete and nonsequential sites. (a) A slow deep Ba2+ site that occludes the channel pore and could be simulated by a model of voltage-dependent block. (b) A fast superficial Ba2+ site that barely contributes to channel block and mostly affects channel gating by shifting rightward the voltage dependence of activation, slowing activation, speeding up deactivation kinetics, and inhibiting channel inactivation. A model of voltage-dependent block cannot predict the complex impact of Ba2+ on channel gating in low external K+ solutions. Ba2+ binding to this superficial site likely modifies the gating transitions states of KCNQ1. Both sites appear to reside in the permeation pathway as high external K+ attenuates Ba2+ inhibition of channel conductance and abolishes its impact on channel gating. Our data suggest that despite the high degree of homology of the pore region among the various K+ channels, KCNQ1 channels display significant structural and functional uniqueness.

Original languageEnglish
Pages (from-to)83-102
Number of pages20
JournalJournal of General Physiology
Volume124
Issue number1
DOIs
StatePublished - Jul 2004

Keywords

  • Channel gating
  • Inactivation
  • Ion channels
  • Outer vestibule
  • Permeation

Fingerprint

Dive into the research topics of 'External barium affects the gating of KCNQ1 potassium channels and produces a pore block via two discrete sites'. Together they form a unique fingerprint.

Cite this