Mechanism underlying slow kinetics of the OFF gating current in Shaker potassium channel

Biophysical Journal
A Melishchuk, C M Armstrong

Abstract

Based on the structure of the KcsA potassium channel, the Shaker K+ channel is thought to have, near the middle of the membrane, a cavity that can be occupied by a permeant or a blocking cation. We have studied the interaction between cations in the cavity and the activation gate of the channel, using a set of monovalent cations together with Shaker mutants that modify the structure of the cavity. Our results show that reducing the size of the side chain at position 470 makes it possible for the mutant channel, unlike native Shaker, to close with tetraethylammonium (TEA+) or the long-chain TEA-derivative C10+ trapped inside the channel. Neither I470 mutants nor Shaker can close when N-methyl-glucamine (NMG+) is in the channel, even though this ion is smaller than C10+. Apparently, the carbohydrate side chain of NMG+ prevents gate closing. Gating currents recorded from Shaker and I470C were measured in the presence of different intracellular cations to further analyze the interaction of cations with the gate. Our results suggest that the cavity in Shaker is so small that even permeant cations like Rb+ or Cs+ must leave the cavity before the channel gate can close.

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Citations

Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Morten Ø JensenDavid E Shaw
Oct 15, 2003·The Journal of General Physiology·Manana SukharevaKenton J Swartz
May 19, 2004·The Journal of General Physiology·Jon T SackWilliam F Gilly
Jun 16, 2004·The Journal of General Physiology·Weiyan Li, Richard W Aldrich
Sep 15, 2004·The Journal of General Physiology·Tetsuya KitaguchiKenton J Swartz
Jul 19, 2006·The Journal of General Physiology·Evan C Ray, Carol Deutsch
Apr 18, 2007·The Journal of General Physiology·Gyorgy Panyi, Carol Deutsch
Oct 29, 2008·The Journal of General Physiology·Andrés Jara-OsegueraLeón D Islas
Apr 1, 2009·The Journal of General Physiology·Zhuren WangDavid Fedida
Oct 17, 2012·The Journal of General Physiology·Samuel J GoodchildDavid Fedida
Aug 30, 2012·The Journal of General Physiology·Vivek GargMichael C Sanguinetti
Mar 13, 2013·The Journal of General Physiology·Zhuren WangDavid Fedida
Jan 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Froylan Gomez-LagunasClay M Armstrong
Mar 27, 2015·Biophysical Journal·Samuel J GoodchildDavid Fedida
Jan 15, 2008·Biophysical Journal·Göran KlementFredrik Elinder
Sep 22, 2015·Nature Neuroscience·Mufeng LiKenton J Swartz
Jan 4, 2012·The European Journal of Neuroscience·Martin B GillDavid S Bredt
Mar 28, 2006·Biochimica Et Biophysica Acta·Xiao-Qing DaiXing-Zhen Chen
Jun 26, 2003·Science's STKE : Signal Transduction Knowledge Environment·Clay M Armstrong
Apr 1, 2003·The Journal of Physiology·Jill Thompson, Ted Begenisich
Nov 7, 2018·The Journal of General Physiology·Drew C TilleyJon T Sack

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