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Zn 2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels
The essential cation zinc (Zn 2+) blocks voltage-dependent calcium channels in several cell types, which exhibit different sensitivities to Zn 2+. The specificity of the Zn 2+ effect on voltage-dependent calcium channel subtypes has not been systematically investigated. In this study, we used a tran...
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Published in: | Biophysical journal 2007, Vol.93 (4), p.1175-1183 |
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container_title | Biophysical journal |
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creator | Sun, Hong-Shuo Hui, Kwokyin Lee, David.W.K. Feng, Zhong-Ping |
description | The essential cation zinc (Zn
2+) blocks voltage-dependent calcium channels in several cell types, which exhibit different sensitivities to Zn
2+. The specificity of the Zn
2+ effect on voltage-dependent calcium channel subtypes has not been systematically investigated. In this study, we used a transient protein expression system to determine the Zn
2+ effect on low- and high-voltage activated channels. We found that in Ba
2+, the IC
50 value of Zn
2+ was
α
1-subunit-dependent with lowest value for Ca
V1.2, and highest for Ca
V3.1; the sensitivity of the channels to Zn
2+ was approximately ranked as Ca
V1.2
>
Ca
V3.2
>
Ca
V2.3
>
Ca
V2.2
=
Ca
V 2.1
≥
Ca
V3.3
=
Ca
V3.1. Although the Ca
V2.2 and Ca
V3.1 channels had similar IC
50 for Zn
2+ in Ba
2+, the Ca
V2.2, but not Ca
V3.1 channels, had ∼10-fold higher IC
50 to Zn
2+ in Ca
2+. The reduced sensitivity of Ca
V2.2 channels to Zn
2+ in Ca
2+ was partially reversed by disrupting a putative EF-hand motif located external to the selectivity filter EEEE locus. Thus, our findings support the notion that the Zn
2+ block, mediated by multiple mechanisms, may depend on conformational changes surrounding the
α
1 pore regions. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of zinc on various Ca
2+ channel subtypes. |
doi_str_mv | 10.1529/biophysj.106.103333 |
format | article |
fullrecord | <record><control><sourceid>elsevier</sourceid><recordid>TN_cdi_elsevier_sciencedirect_doi_10_1529_biophysj_106_103333</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006349507713759</els_id><sourcerecordid>S0006349507713759</sourcerecordid><originalsourceid>FETCH-elsevier_sciencedirect_doi_10_1529_biophysj_106_1033333</originalsourceid><addsrcrecordid>eNqljkFrAjEQhYNUcKv-Ai9zL7GTXXephx7KonjwVvHgJcTs6I6sSTGpxX_fSNtf0AePB-_NwCfEROFUlfn8ec_-o72F01RhlVwk9USmylkuEV-qB5EhYiWL2bwciMcQTogqL1FlYrFzkD_BO7nAka8cb-APsOJjK8G4Btb-S259F82R4M2mCxOpgdp0lj_PULfGOerCSPQPpgs0_s2heF0uNvVKpo2uTBcdLJOz1PCFbNSNZ61Q39n1H3sqKv3DXvz3_xtsz1Rj</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Zn 2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels</title><source>PubMed Central</source><creator>Sun, Hong-Shuo ; Hui, Kwokyin ; Lee, David.W.K. ; Feng, Zhong-Ping</creator><creatorcontrib>Sun, Hong-Shuo ; Hui, Kwokyin ; Lee, David.W.K. ; Feng, Zhong-Ping</creatorcontrib><description>The essential cation zinc (Zn
2+) blocks voltage-dependent calcium channels in several cell types, which exhibit different sensitivities to Zn
2+. The specificity of the Zn
2+ effect on voltage-dependent calcium channel subtypes has not been systematically investigated. In this study, we used a transient protein expression system to determine the Zn
2+ effect on low- and high-voltage activated channels. We found that in Ba
2+, the IC
50 value of Zn
2+ was
α
1-subunit-dependent with lowest value for Ca
V1.2, and highest for Ca
V3.1; the sensitivity of the channels to Zn
2+ was approximately ranked as Ca
V1.2
>
Ca
V3.2
>
Ca
V2.3
>
Ca
V2.2
=
Ca
V 2.1
≥
Ca
V3.3
=
Ca
V3.1. Although the Ca
V2.2 and Ca
V3.1 channels had similar IC
50 for Zn
2+ in Ba
2+, the Ca
V2.2, but not Ca
V3.1 channels, had ∼10-fold higher IC
50 to Zn
2+ in Ca
2+. The reduced sensitivity of Ca
V2.2 channels to Zn
2+ in Ca
2+ was partially reversed by disrupting a putative EF-hand motif located external to the selectivity filter EEEE locus. Thus, our findings support the notion that the Zn
2+ block, mediated by multiple mechanisms, may depend on conformational changes surrounding the
α
1 pore regions. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of zinc on various Ca
2+ channel subtypes.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1529/biophysj.106.103333</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Biophysical journal, 2007, Vol.93 (4), p.1175-1183</ispartof><rights>2007 The Biophysical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4023,27922,27923,27924</link.rule.ids></links><search><creatorcontrib>Sun, Hong-Shuo</creatorcontrib><creatorcontrib>Hui, Kwokyin</creatorcontrib><creatorcontrib>Lee, David.W.K.</creatorcontrib><creatorcontrib>Feng, Zhong-Ping</creatorcontrib><title>Zn 2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels</title><title>Biophysical journal</title><description>The essential cation zinc (Zn
2+) blocks voltage-dependent calcium channels in several cell types, which exhibit different sensitivities to Zn
2+. The specificity of the Zn
2+ effect on voltage-dependent calcium channel subtypes has not been systematically investigated. In this study, we used a transient protein expression system to determine the Zn
2+ effect on low- and high-voltage activated channels. We found that in Ba
2+, the IC
50 value of Zn
2+ was
α
1-subunit-dependent with lowest value for Ca
V1.2, and highest for Ca
V3.1; the sensitivity of the channels to Zn
2+ was approximately ranked as Ca
V1.2
>
Ca
V3.2
>
Ca
V2.3
>
Ca
V2.2
=
Ca
V 2.1
≥
Ca
V3.3
=
Ca
V3.1. Although the Ca
V2.2 and Ca
V3.1 channels had similar IC
50 for Zn
2+ in Ba
2+, the Ca
V2.2, but not Ca
V3.1 channels, had ∼10-fold higher IC
50 to Zn
2+ in Ca
2+. The reduced sensitivity of Ca
V2.2 channels to Zn
2+ in Ca
2+ was partially reversed by disrupting a putative EF-hand motif located external to the selectivity filter EEEE locus. Thus, our findings support the notion that the Zn
2+ block, mediated by multiple mechanisms, may depend on conformational changes surrounding the
α
1 pore regions. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of zinc on various Ca
2+ channel subtypes.</description><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqljkFrAjEQhYNUcKv-Ai9zL7GTXXephx7KonjwVvHgJcTs6I6sSTGpxX_fSNtf0AePB-_NwCfEROFUlfn8ec_-o72F01RhlVwk9USmylkuEV-qB5EhYiWL2bwciMcQTogqL1FlYrFzkD_BO7nAka8cb-APsOJjK8G4Btb-S259F82R4M2mCxOpgdp0lj_PULfGOerCSPQPpgs0_s2heF0uNvVKpo2uTBcdLJOz1PCFbNSNZ61Q39n1H3sqKv3DXvz3_xtsz1Rj</recordid><startdate>2007</startdate><enddate>2007</enddate><creator>Sun, Hong-Shuo</creator><creator>Hui, Kwokyin</creator><creator>Lee, David.W.K.</creator><creator>Feng, Zhong-Ping</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope></search><sort><creationdate>2007</creationdate><title>Zn 2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels</title><author>Sun, Hong-Shuo ; Hui, Kwokyin ; Lee, David.W.K. ; Feng, Zhong-Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-elsevier_sciencedirect_doi_10_1529_biophysj_106_1033333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Hong-Shuo</creatorcontrib><creatorcontrib>Hui, Kwokyin</creatorcontrib><creatorcontrib>Lee, David.W.K.</creatorcontrib><creatorcontrib>Feng, Zhong-Ping</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Hong-Shuo</au><au>Hui, Kwokyin</au><au>Lee, David.W.K.</au><au>Feng, Zhong-Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Zn 2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels</atitle><jtitle>Biophysical journal</jtitle><date>2007</date><risdate>2007</risdate><volume>93</volume><issue>4</issue><spage>1175</spage><epage>1183</epage><pages>1175-1183</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>The essential cation zinc (Zn
2+) blocks voltage-dependent calcium channels in several cell types, which exhibit different sensitivities to Zn
2+. The specificity of the Zn
2+ effect on voltage-dependent calcium channel subtypes has not been systematically investigated. In this study, we used a transient protein expression system to determine the Zn
2+ effect on low- and high-voltage activated channels. We found that in Ba
2+, the IC
50 value of Zn
2+ was
α
1-subunit-dependent with lowest value for Ca
V1.2, and highest for Ca
V3.1; the sensitivity of the channels to Zn
2+ was approximately ranked as Ca
V1.2
>
Ca
V3.2
>
Ca
V2.3
>
Ca
V2.2
=
Ca
V 2.1
≥
Ca
V3.3
=
Ca
V3.1. Although the Ca
V2.2 and Ca
V3.1 channels had similar IC
50 for Zn
2+ in Ba
2+, the Ca
V2.2, but not Ca
V3.1 channels, had ∼10-fold higher IC
50 to Zn
2+ in Ca
2+. The reduced sensitivity of Ca
V2.2 channels to Zn
2+ in Ca
2+ was partially reversed by disrupting a putative EF-hand motif located external to the selectivity filter EEEE locus. Thus, our findings support the notion that the Zn
2+ block, mediated by multiple mechanisms, may depend on conformational changes surrounding the
α
1 pore regions. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of zinc on various Ca
2+ channel subtypes.</abstract><pub>Elsevier Inc</pub><doi>10.1529/biophysj.106.103333</doi><oa>free_for_read</oa></addata></record> |
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source | PubMed Central |
title | Zn 2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels |
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