Grafting voltage and pharmacological sensitivity in potassium channels

A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number...

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Published inCell research Vol. 26; no. 8; pp. 935 - 945
Main Authors Lan, Xi, Fan, Chunyan, Ji, Wei, Tian, Fuyun, Xu, Tao, Gao, Zhaobing
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.08.2016
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Abstract A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.
AbstractList A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.
A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.
Author Xi Lan Chunyan Fan Wei Ji Fuyun Tian Tao Xu Zhaobing Gao
AuthorAffiliation CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 5 Datun Road, Beijing 100101, China University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China
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crossref_primary_10_1093_biolre_ioz096
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DocumentTitleAlternate Grafting voltage and pharmacological sensitivity in potassium channels
One VSD gates a voltage-dependent Kv7.1-TASK3 channel
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K2P channels
voltage-gated channels
voltage-sensing domain
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Notes voltage-gated channels; K2P channels; voltage-sensing domain; graft
A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.
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These two authors contributed equally to this work.
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Snippet A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We...
A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We...
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SubjectTerms 631/57/2272
631/80/86
631/92/269/1151
Animals
Biomedical and Life Sciences
Cell Biology
CHO Cells
Cricetinae
Cricetulus
Humans
Hydrogen-Ion Concentration
Ion Channel Gating - drug effects
Life Sciences
Membrane Transport Modulators - pharmacology
Original
original-article
Potassium Channels - chemistry
Potassium Channels - metabolism
Potassium Channels, Tandem Pore Domain - metabolism
Protein Domains
嫁接
敏感性
电压传感
电压依赖性
电压门控
离子通道
药理
钾通道
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Title Grafting voltage and pharmacological sensitivity in potassium channels
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