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Characterization of voltage-gated sodium-channel blockers by electrical stimulation and fluorescence detection of membrane potential
Voltage-gated ion channels regulate many physiological functions and are targets for a number of drugs. Patch-clamp electrophysiology is the standard method for measuring channel activity because it fulfils the requirements for voltage control, repetitive stimulation and high temporal resolution, bu...
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Published in: | Nature biotechnology 2006-04, Vol.24 (4), p.439-446 |
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container_title | Nature biotechnology |
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creator | González, Jesús E Huang, Chien-Jung Harootunian, Alec Maher, Michael P Quan, Catherine Raj, Christopher D McCormack, Ken Numann, Randal Negulescu, Paul A |
description | Voltage-gated ion channels regulate many physiological functions and are targets for a number of drugs. Patch-clamp electrophysiology is the standard method for measuring channel activity because it fulfils the requirements for voltage control, repetitive stimulation and high temporal resolution, but it is laborious and costly. Here we report an electro-optical technology and automated instrument, called the electrical stimulation voltage ion probe reader (E-VIPR), that measures the activity of voltage-gated ion channels using extracellular electrical field stimulation and voltage-sensitive fluorescent probes. We demonstrate that E-VIPR can sensitively detect drug potency and mechanism of block on the neuronal human type III voltage-gated sodium channel expressed in human embryonic kidney cells. Results are compared with voltage-clamp and show that E-VIPR provides sensitive and information-rich compound blocking activity. Furthermore, we screened ∼400 drugs and observed sodium channel–blocking activity for ∼25% of them, including the antidepressants sertraline (Zoloft) and paroxetine (Paxil). |
doi_str_mv | 10.1038/nbt1194 |
format | article |
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Patch-clamp electrophysiology is the standard method for measuring channel activity because it fulfils the requirements for voltage control, repetitive stimulation and high temporal resolution, but it is laborious and costly. Here we report an electro-optical technology and automated instrument, called the electrical stimulation voltage ion probe reader (E-VIPR), that measures the activity of voltage-gated ion channels using extracellular electrical field stimulation and voltage-sensitive fluorescent probes. We demonstrate that E-VIPR can sensitively detect drug potency and mechanism of block on the neuronal human type III voltage-gated sodium channel expressed in human embryonic kidney cells. Results are compared with voltage-clamp and show that E-VIPR provides sensitive and information-rich compound blocking activity. Furthermore, we screened ∼400 drugs and observed sodium channel–blocking activity for ∼25% of them, including the antidepressants sertraline (Zoloft) and paroxetine (Paxil).</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt1194</identifier><identifier>PMID: 16550174</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Analysis ; Antidepressants ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Cells, Cultured ; Drug Design ; Electric fields ; Electric Stimulation - methods ; General pharmacology ; Humans ; Ion Channel Gating - drug effects ; Ion Channel Gating - physiology ; Ions ; Kidneys ; Life Sciences ; Measurement techniques ; Medical sciences ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Microscopy, Fluorescence - methods ; Neurons - drug effects ; Neurons - physiology ; Patch-Clamp Techniques - methods ; Pharmaceutical Preparations - administration & dosage ; Pharmacology. Drug treatments ; Physiology ; Probes ; Research methodology ; Sodium ; Sodium Channels - drug effects ; Sodium Channels - physiology</subject><ispartof>Nature biotechnology, 2006-04, Vol.24 (4), p.439-446</ispartof><rights>Springer Nature America, Inc. 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c627t-4478a27ebe365e4c593092ff2f6d5952d113ca6cbfab0fe3c98f968fa0fdbdeb3</citedby><cites>FETCH-LOGICAL-c627t-4478a27ebe365e4c593092ff2f6d5952d113ca6cbfab0fe3c98f968fa0fdbdeb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17716715$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16550174$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>González, Jesús E</creatorcontrib><creatorcontrib>Huang, Chien-Jung</creatorcontrib><creatorcontrib>Harootunian, Alec</creatorcontrib><creatorcontrib>Maher, Michael P</creatorcontrib><creatorcontrib>Quan, Catherine</creatorcontrib><creatorcontrib>Raj, Christopher D</creatorcontrib><creatorcontrib>McCormack, Ken</creatorcontrib><creatorcontrib>Numann, Randal</creatorcontrib><creatorcontrib>Negulescu, Paul A</creatorcontrib><title>Characterization of voltage-gated sodium-channel blockers by electrical stimulation and fluorescence detection of membrane potential</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>Voltage-gated ion channels regulate many physiological functions and are targets for a number of drugs. Patch-clamp electrophysiology is the standard method for measuring channel activity because it fulfils the requirements for voltage control, repetitive stimulation and high temporal resolution, but it is laborious and costly. Here we report an electro-optical technology and automated instrument, called the electrical stimulation voltage ion probe reader (E-VIPR), that measures the activity of voltage-gated ion channels using extracellular electrical field stimulation and voltage-sensitive fluorescent probes. We demonstrate that E-VIPR can sensitively detect drug potency and mechanism of block on the neuronal human type III voltage-gated sodium channel expressed in human embryonic kidney cells. Results are compared with voltage-clamp and show that E-VIPR provides sensitive and information-rich compound blocking activity. 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Academic</collection><collection>Aqualine</collection><collection>Water Resources Abstracts</collection><jtitle>Nature biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>González, Jesús E</au><au>Huang, Chien-Jung</au><au>Harootunian, Alec</au><au>Maher, Michael P</au><au>Quan, Catherine</au><au>Raj, Christopher D</au><au>McCormack, Ken</au><au>Numann, Randal</au><au>Negulescu, Paul A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of voltage-gated sodium-channel blockers by electrical stimulation and fluorescence detection of membrane potential</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>24</volume><issue>4</issue><spage>439</spage><epage>446</epage><pages>439-446</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><coden>NABIF9</coden><abstract>Voltage-gated ion channels regulate many physiological functions and are targets for a number of drugs. Patch-clamp electrophysiology is the standard method for measuring channel activity because it fulfils the requirements for voltage control, repetitive stimulation and high temporal resolution, but it is laborious and costly. Here we report an electro-optical technology and automated instrument, called the electrical stimulation voltage ion probe reader (E-VIPR), that measures the activity of voltage-gated ion channels using extracellular electrical field stimulation and voltage-sensitive fluorescent probes. We demonstrate that E-VIPR can sensitively detect drug potency and mechanism of block on the neuronal human type III voltage-gated sodium channel expressed in human embryonic kidney cells. Results are compared with voltage-clamp and show that E-VIPR provides sensitive and information-rich compound blocking activity. Furthermore, we screened ∼400 drugs and observed sodium channel–blocking activity for ∼25% of them, including the antidepressants sertraline (Zoloft) and paroxetine (Paxil).</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>16550174</pmid><doi>10.1038/nbt1194</doi><tpages>8</tpages></addata></record> |
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subjects | Agriculture Analysis Antidepressants Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Cells, Cultured Drug Design Electric fields Electric Stimulation - methods General pharmacology Humans Ion Channel Gating - drug effects Ion Channel Gating - physiology Ions Kidneys Life Sciences Measurement techniques Medical sciences Membrane Potentials - drug effects Membrane Potentials - physiology Microscopy, Fluorescence - methods Neurons - drug effects Neurons - physiology Patch-Clamp Techniques - methods Pharmaceutical Preparations - administration & dosage Pharmacology. Drug treatments Physiology Probes Research methodology Sodium Sodium Channels - drug effects Sodium Channels - physiology |
title | Characterization of voltage-gated sodium-channel blockers by electrical stimulation and fluorescence detection of membrane potential |
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