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New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA
We present in this work a structural model of the open IKCa (K(Ca)3.1) channel derived by homology modeling from the MthK channel structure, and used this model to compute the transmembrane potential profile along the channel pore. This analysis showed that the selectivity filter and the region exte...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2233899/ https://www.ncbi.nlm.nih.gov/pubmed/15452196 http://dx.doi.org/10.1085/jgp.200409145 |
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author | Banderali, Umberto Klein, Hélène Garneau, Line Simoes, Manuel Parent, Lucie Sauvé, Rémy |
author_facet | Banderali, Umberto Klein, Hélène Garneau, Line Simoes, Manuel Parent, Lucie Sauvé, Rémy |
author_sort | Banderali, Umberto |
collection | PubMed |
description | We present in this work a structural model of the open IKCa (K(Ca)3.1) channel derived by homology modeling from the MthK channel structure, and used this model to compute the transmembrane potential profile along the channel pore. This analysis showed that the selectivity filter and the region extending from the channel inner cavity to the internal medium should respectively account for 81% and 16% of the transmembrane potential difference. We found however that the voltage dependence of the IKCa block by the quaternary ammonium ion TBA applied internally is compatible with an apparent electrical distance δ of 0.49 ± 0.02 (n = 6) for negative potentials. To reconcile this observation with the electrostatic potential profile predicted for the channel pore, we modeled the IKCa block by TBA assuming that the voltage dependence of the block is governed by both the difference in potential between the channel cavity and the internal medium, and the potential profile along the selectivity filter region through an effect on the filter ion occupancy states. The resulting model predicts that δ should be voltage dependent, being larger at negative than positive potentials. The model also indicates that raising the internal K(+) concentration should decrease the value of δ measured at negative potentials independently of the external K(+) concentration, whereas raising the external K(+) concentration should minimally affect δ for concentrations >50 mM. All these predictions are born out by our current experimental results. Finally, we found that the substitutions V275C and V275A increased the voltage sensitivity of the TBA block, suggesting that TBA could move further into the pore, thus leading to stronger interactions between TBA and the ions in the selectivity filter. Globally, these results support a model whereby the voltage dependence of the TBA block in IKCa is mainly governed by the voltage dependence of the ion occupancy states of the selectivity filter. |
format | Text |
id | pubmed-2233899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22338992008-03-21 New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA Banderali, Umberto Klein, Hélène Garneau, Line Simoes, Manuel Parent, Lucie Sauvé, Rémy J Gen Physiol Article We present in this work a structural model of the open IKCa (K(Ca)3.1) channel derived by homology modeling from the MthK channel structure, and used this model to compute the transmembrane potential profile along the channel pore. This analysis showed that the selectivity filter and the region extending from the channel inner cavity to the internal medium should respectively account for 81% and 16% of the transmembrane potential difference. We found however that the voltage dependence of the IKCa block by the quaternary ammonium ion TBA applied internally is compatible with an apparent electrical distance δ of 0.49 ± 0.02 (n = 6) for negative potentials. To reconcile this observation with the electrostatic potential profile predicted for the channel pore, we modeled the IKCa block by TBA assuming that the voltage dependence of the block is governed by both the difference in potential between the channel cavity and the internal medium, and the potential profile along the selectivity filter region through an effect on the filter ion occupancy states. The resulting model predicts that δ should be voltage dependent, being larger at negative than positive potentials. The model also indicates that raising the internal K(+) concentration should decrease the value of δ measured at negative potentials independently of the external K(+) concentration, whereas raising the external K(+) concentration should minimally affect δ for concentrations >50 mM. All these predictions are born out by our current experimental results. Finally, we found that the substitutions V275C and V275A increased the voltage sensitivity of the TBA block, suggesting that TBA could move further into the pore, thus leading to stronger interactions between TBA and the ions in the selectivity filter. Globally, these results support a model whereby the voltage dependence of the TBA block in IKCa is mainly governed by the voltage dependence of the ion occupancy states of the selectivity filter. The Rockefeller University Press 2004-10 /pmc/articles/PMC2233899/ /pubmed/15452196 http://dx.doi.org/10.1085/jgp.200409145 Text en Copyright © 2004, The Rockefeller University Press 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 Banderali, Umberto Klein, Hélène Garneau, Line Simoes, Manuel Parent, Lucie Sauvé, Rémy New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA |
title | New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA |
title_full | New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA |
title_fullStr | New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA |
title_full_unstemmed | New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA |
title_short | New Insights on the Voltage Dependence of the K(Ca)3.1 Channel Block by Internal TBA |
title_sort | new insights on the voltage dependence of the k(ca)3.1 channel block by internal tba |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2233899/ https://www.ncbi.nlm.nih.gov/pubmed/15452196 http://dx.doi.org/10.1085/jgp.200409145 |
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