A tyrosine substitution in the cavity wall of a k channel induces an inverted inactivation

Biophysical Journal
Göran KlementFredrik Elinder

Abstract

Ion permeation and gating kinetics of voltage-gated K channels critically depend on the amino-acid composition of the cavity wall. Residue 470 in the Shaker K channel is an isoleucine, making the cavity volume in a closed channel insufficiently large for a hydrated K(+) ion. In the cardiac human ether-a-go-go-related gene channel, which exhibits slow activation and fast inactivation, the corresponding residue is tyrosine. To explore the role of a tyrosine at this position in the Shaker channel, we studied I470Y. The activation became slower, and the inactivation faster and more complex. At +60 mV the channel inactivated with two distinct rates (tau(1) = 20 ms, tau(2) = 400 ms). Experiments with tetraethylammonium and high K(+) concentrations suggest that the slower component was of the P/C-type. In addition, an inactivation component with inverted voltage dependence was introduced. A step to -40 mV inactivates the channel with a time constant of 500 ms. Negative voltage steps do not cause the channel to recover from this inactivated state (tau > 10 min), whereas positive voltage steps quickly do (tau = 2 ms at +60 mV). The experimental findings can be explained by a simple branched kinetic model with two inactivation pathways f...Continue Reading

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Citations

Sep 20, 2011·Chemical Reviews·Jeeyeon Lee, Nina M Goodey
Nov 26, 2008·The Journal of General Physiology·Vivian González-PérezDavid Naranjo
Aug 30, 2012·The Journal of General Physiology·Vivek GargMichael C Sanguinetti
Jan 28, 2010·ChemMedChem·Anna StaryBert L de Groot

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