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

The Journal of General Physiology
Gilad GiborB Attali

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 KCNQ1 channels. We assessed the Ba(2+) binding kinetics and the concentration and voltage dependence of Ba(2+) steady-state block. Our results indicate that extracellular Ba(2+) 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 Ba(2+) site that occludes the channel pore and could be simulated by a model of voltage-dependent block. (b) A fast superficial Ba(2+) 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 Ba(2+) on channel gating in low external K(+) solutions. Ba(2+) binding to this superficial site likely modifies the gating transitions states of KCNQ1. Both sites appear to r...Continue Reading

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Citations

Jun 24, 2010·Biochemistry·Andrea S Moomaw, Michael E Maguire
Feb 1, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Zuojun Ren, Clive M Baumgarten
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Methods Mentioned

BETA
electrophoresis

Software Mentioned

Clampfit
GraphPad
Excel
SigmaPlot
Berkeley Madonna
pCLAMP
Prism

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