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Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating

Small organic molecules, like quaternary ammonium compounds, have long been used to probe both the permeation and gating of voltage-dependent K(+) channels. For most K(+) channels, intracellularly applied quaternary ammonium (QA) compounds such as tetraethylammonium (TEA) and decyltriethylammonium (...

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Autores principales: Holmgren, Miguel, Smith, Paula L., Yellen, Gary
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217058/
https://www.ncbi.nlm.nih.gov/pubmed/9154902
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author Holmgren, Miguel
Smith, Paula L.
Yellen, Gary
author_facet Holmgren, Miguel
Smith, Paula L.
Yellen, Gary
author_sort Holmgren, Miguel
collection PubMed
description Small organic molecules, like quaternary ammonium compounds, have long been used to probe both the permeation and gating of voltage-dependent K(+) channels. For most K(+) channels, intracellularly applied quaternary ammonium (QA) compounds such as tetraethylammonium (TEA) and decyltriethylammonium (C(10)) behave primarily as open channel blockers: they can enter the channel only when it is open, and they must dissociate before the channel can close. In some cases, it is possible to force the channel to close with a QA blocker still bound, with the result that the blocker is “trapped.” Armstrong (J. Gen. Physiol. 58:413–437) found that at very negative voltages, squid axon K(+) channels exhibited a slow phase of recovery from QA blockade consistent with such trapping. In our studies on the cloned Shaker channel, we find that wild-type channels can trap neither TEA nor C(10), but channels with a point mutation in S6 can trap either compound very efficiently. The trapping occurs with very little change in the energetics of channel gating, suggesting that in these channels the gate may function as a trap door or hinged lid that occludes access from the intracellular solution to the blocker site and to the narrow ion-selective pore.
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spelling pubmed-22170582008-04-22 Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating Holmgren, Miguel Smith, Paula L. Yellen, Gary J Gen Physiol Article Small organic molecules, like quaternary ammonium compounds, have long been used to probe both the permeation and gating of voltage-dependent K(+) channels. For most K(+) channels, intracellularly applied quaternary ammonium (QA) compounds such as tetraethylammonium (TEA) and decyltriethylammonium (C(10)) behave primarily as open channel blockers: they can enter the channel only when it is open, and they must dissociate before the channel can close. In some cases, it is possible to force the channel to close with a QA blocker still bound, with the result that the blocker is “trapped.” Armstrong (J. Gen. Physiol. 58:413–437) found that at very negative voltages, squid axon K(+) channels exhibited a slow phase of recovery from QA blockade consistent with such trapping. In our studies on the cloned Shaker channel, we find that wild-type channels can trap neither TEA nor C(10), but channels with a point mutation in S6 can trap either compound very efficiently. The trapping occurs with very little change in the energetics of channel gating, suggesting that in these channels the gate may function as a trap door or hinged lid that occludes access from the intracellular solution to the blocker site and to the narrow ion-selective pore. The Rockefeller University Press 1997-05-01 /pmc/articles/PMC2217058/ /pubmed/9154902 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Holmgren, Miguel
Smith, Paula L.
Yellen, Gary
Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating
title Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating
title_full Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating
title_fullStr Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating
title_full_unstemmed Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating
title_short Trapping of Organic Blockers by Closing of Voltage-dependent K(+) Channels : Evidence for a Trap Door Mechanism of Activation Gating
title_sort trapping of organic blockers by closing of voltage-dependent k(+) channels : evidence for a trap door mechanism of activation gating
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217058/
https://www.ncbi.nlm.nih.gov/pubmed/9154902
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