Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration
A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited...
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| Veröffentlicht in: | Biological & Pharmaceutical Bulletin 2005, Vol.28(4), pp.657-660 |
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| creator | Eun, Jae Soon Park, Jung Ah Choi, Bok Hee Cho, Sun Kyung Kim, Dae Keun Kwak, Yong Geun |
| description | A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC50 value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between −40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation. |
| doi_str_mv | 10.1248/bpb.28.657 |
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Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC50 value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between −40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.28.657</identifier><identifier>PMID: 15802805</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Action Potentials - drug effects ; Action Potentials - physiology ; Angelica ; Angelica dahurica ; Animals ; antiarrhythmic drug ; Cell Line ; Dose-Response Relationship, Drug ; Furocoumarins - chemistry ; Furocoumarins - pharmacology ; Heart - physiology ; hKv1.5 channel blocker ; Humans ; In Vitro Techniques ; Molecular Structure ; oxypeucedanin ; Potassium Channel Blockers - chemistry ; Potassium Channel Blockers - pharmacology ; Potassium Channels, Voltage-Gated - drug effects ; Potassium Channels, Voltage-Gated - physiology ; Rats</subject><ispartof>Biological and Pharmaceutical Bulletin, 2005, Vol.28(4), pp.657-660</ispartof><rights>2005 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c685t-8acd7d379e0efdcae09285376d82dbd474ede59079c2f81a9795751c4f2d9c143</citedby><cites>FETCH-LOGICAL-c685t-8acd7d379e0efdcae09285376d82dbd474ede59079c2f81a9795751c4f2d9c143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15802805$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eun, Jae Soon</creatorcontrib><creatorcontrib>Park, Jung Ah</creatorcontrib><creatorcontrib>Choi, Bok Hee</creatorcontrib><creatorcontrib>Cho, Sun Kyung</creatorcontrib><creatorcontrib>Kim, Dae Keun</creatorcontrib><creatorcontrib>Kwak, Yong Geun</creatorcontrib><creatorcontrib>aCollege of Pharmacy</creatorcontrib><creatorcontrib>bDepartment of Pharmacology</creatorcontrib><creatorcontrib>Woosuk University</creatorcontrib><creatorcontrib>Chonbuk National University Medical School</creatorcontrib><title>Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration</title><title>Biological & Pharmaceutical Bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC50 value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between −40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.</description><subject>Action Potentials - drug effects</subject><subject>Action Potentials - physiology</subject><subject>Angelica</subject><subject>Angelica dahurica</subject><subject>Animals</subject><subject>antiarrhythmic drug</subject><subject>Cell Line</subject><subject>Dose-Response Relationship, Drug</subject><subject>Furocoumarins - chemistry</subject><subject>Furocoumarins - pharmacology</subject><subject>Heart - physiology</subject><subject>hKv1.5 channel blocker</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Molecular Structure</subject><subject>oxypeucedanin</subject><subject>Potassium Channel Blockers - chemistry</subject><subject>Potassium Channel Blockers - pharmacology</subject><subject>Potassium Channels, Voltage-Gated - drug effects</subject><subject>Potassium Channels, Voltage-Gated - physiology</subject><subject>Rats</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE9v1DAQxS0EokvhwgdAkZA4VMoydvz3BFVbCqJSOcDZcuwJzSprL3GC6LfHUbZU4jIjvfnNm9Ej5DWFLWVcv28P7ZbprRTqCdnQhqtaMCqekg0YqmtJhT4hL3LeAYAC1jwnJ0UCpkFsyMerrkM_5Sp11e2f-wPOHoOLfaxSrO6-_qZbUbkYqnM_9UX5liaMU--G6nIe3SK9JM86N2R8deyn5Menq-8Xn-ub2-svF-c3tZdaTLV2PqjQKIOAXfAOwTAtGiWDZqENXHEMKAwo41mnqTPKCCWo5x0LxlPenJJ3q-9hTL9mzJPd99njMLiIac5WKiENN7KAb_8Dd2keY_nNUs5Nwylji93ZSvkx5TxiZw9jv3fjvaVgl1RtSdUybUuqBX5ztJzbPYZH9BhjAa5XoEx774YUhz7i42GfVdunIVkGICwsS9wCNRaKfSkSKChpKC1OH1anXZ7cT_x3yo1T7wd8-IqvZdl-mPg7N1qMzV9ZYJ3W</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Eun, Jae Soon</creator><creator>Park, Jung Ah</creator><creator>Choi, Bok Hee</creator><creator>Cho, Sun Kyung</creator><creator>Kim, Dae Keun</creator><creator>Kwak, Yong Geun</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20050401</creationdate><title>Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration</title><author>Eun, Jae Soon ; Park, Jung Ah ; Choi, Bok Hee ; Cho, Sun Kyung ; Kim, Dae Keun ; Kwak, Yong Geun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c685t-8acd7d379e0efdcae09285376d82dbd474ede59079c2f81a9795751c4f2d9c143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Action Potentials - drug effects</topic><topic>Action Potentials - physiology</topic><topic>Angelica</topic><topic>Angelica dahurica</topic><topic>Animals</topic><topic>antiarrhythmic drug</topic><topic>Cell Line</topic><topic>Dose-Response Relationship, Drug</topic><topic>Furocoumarins - chemistry</topic><topic>Furocoumarins - pharmacology</topic><topic>Heart - physiology</topic><topic>hKv1.5 channel blocker</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Molecular Structure</topic><topic>oxypeucedanin</topic><topic>Potassium Channel Blockers - chemistry</topic><topic>Potassium Channel Blockers - pharmacology</topic><topic>Potassium Channels, Voltage-Gated - drug effects</topic><topic>Potassium Channels, Voltage-Gated - physiology</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eun, Jae Soon</creatorcontrib><creatorcontrib>Park, Jung Ah</creatorcontrib><creatorcontrib>Choi, Bok Hee</creatorcontrib><creatorcontrib>Cho, Sun Kyung</creatorcontrib><creatorcontrib>Kim, Dae Keun</creatorcontrib><creatorcontrib>Kwak, Yong Geun</creatorcontrib><creatorcontrib>aCollege of Pharmacy</creatorcontrib><creatorcontrib>bDepartment of Pharmacology</creatorcontrib><creatorcontrib>Woosuk University</creatorcontrib><creatorcontrib>Chonbuk National University Medical School</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & Pharmaceutical Bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eun, Jae Soon</au><au>Park, Jung Ah</au><au>Choi, Bok Hee</au><au>Cho, Sun Kyung</au><au>Kim, Dae Keun</au><au>Kwak, Yong Geun</au><aucorp>aCollege of Pharmacy</aucorp><aucorp>bDepartment of Pharmacology</aucorp><aucorp>Woosuk University</aucorp><aucorp>Chonbuk National University Medical School</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration</atitle><jtitle>Biological & Pharmaceutical Bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>28</volume><issue>4</issue><spage>657</spage><epage>660</epage><pages>657-660</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC50 value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between −40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. 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| subjects | Action Potentials - drug effects Action Potentials - physiology Angelica Angelica dahurica Animals antiarrhythmic drug Cell Line Dose-Response Relationship, Drug Furocoumarins - chemistry Furocoumarins - pharmacology Heart - physiology hKv1.5 channel blocker Humans In Vitro Techniques Molecular Structure oxypeucedanin Potassium Channel Blockers - chemistry Potassium Channel Blockers - pharmacology Potassium Channels, Voltage-Gated - drug effects Potassium Channels, Voltage-Gated - physiology Rats |
| title | Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration |
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