Evidence for Developmental Changes in Sodium Channel Inactivation Gating and Sodium Channel Block by Phenytoin in Rat Cardiac Myocytes
The voltage-dependent properties of the voltage-activated sodium channel were studied in neonatal (1–2-day-old) and adult rat ventricular cardiac myocytes using the whole-cell variation of the patch-clamp technique (16°C, [Na]i=15 mM, [Na]o=25 mM). The voltage dependence of the sodium conductance-me...
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| Veröffentlicht in: | Circulation research 1991-09, Vol.69 (3), p.644-656 |
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| creator | Xu, You-Qiu Pickoff, Arthur S Clarkson, Craig W |
| description | The voltage-dependent properties of the voltage-activated sodium channel were studied in neonatal (1–2-day-old) and adult rat ventricular cardiac myocytes using the whole-cell variation of the patch-clamp technique (16°C, [Na]i=15 mM, [Na]o=25 mM). The voltage dependence of the sodium conductance-membrane potential relation was similar in both neonatal and adult myocytes except for a difference in slope; the adult sodium conductance-membrane potential relation was slightly more steep. Neonatal cells also differed from adult cells by demonstrating a more negative voltage midpoint of their sodium availability curve, a slower rate of recovery from inactivation at hyperpolarized potentials, and a greater extent of slow inactivation development compared with adult cells. Phenytoin (40 μM) reduced the sodium current in a tonic and use-dependent manner in both adult and neonatal myocytes. However, phenytoin (40 μM) produced significantly more tonic block at negative holding potentials (e.g., −140 mV) in neonatal myocytes (22±5% [mean±SEMI, n=14) than in adult myocytes (10±2%, n=11) (p |
| doi_str_mv | 10.1161/01.res.69.3.644 |
| format | Article |
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The voltage dependence of the sodium conductance-membrane potential relation was similar in both neonatal and adult myocytes except for a difference in slope; the adult sodium conductance-membrane potential relation was slightly more steep. Neonatal cells also differed from adult cells by demonstrating a more negative voltage midpoint of their sodium availability curve, a slower rate of recovery from inactivation at hyperpolarized potentials, and a greater extent of slow inactivation development compared with adult cells. Phenytoin (40 μM) reduced the sodium current in a tonic and use-dependent manner in both adult and neonatal myocytes. However, phenytoin (40 μM) produced significantly more tonic block at negative holding potentials (e.g., −140 mV) in neonatal myocytes (22±5% [mean±SEMI, n=14) than in adult myocytes (10±2%, n=11) (p<0.05). The amplitudes of use-dependent block obtained during trains of 1-second pulses to −20 mV were also significantly greater in neonatal myocytes than in adult myocytes when the diastolic interval was varied over a range of 0.1–1.5 seconds (p<0.05). Definition of the time courses of block development at −20 mV indicated that phenytoin had a slightly higher affinity for inactivated sodium channels in neonatal cells. In addition, the time constant of recovery from use-dependent block by phenytoin was found to be significantly longer in neonatal cells than in adult cells at membrane potentials between −160 and −100 mV (p<0.001). The marked differences in phenytoin effect on cardiac sodium channels in neonatal versus adult rat cardiac myocytes suggest that there may be significant developmental changes in the sodium channel blocking effects of class I antiarrhythmic drugs in cardiac tissue. (Circulation Research 1991;69:644–656)</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.res.69.3.644</identifier><identifier>PMID: 1651816</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Age Factors ; Animals ; Animals, Newborn ; Biological and medical sciences ; cardiac muscle ; Cells, Cultured ; channels ; Fundamental and applied biological sciences. Psychology ; gating ; Heart ; Heart - drug effects ; Heart - physiology ; inactivation ; Membrane Potentials ; Myocardium - cytology ; Myocardium - metabolism ; phenytoin ; Phenytoin - pharmacology ; Rats ; sodium ; Sodium - metabolism ; Sodium Channels - drug effects ; Vertebrates: cardiovascular system</subject><ispartof>Circulation research, 1991-09, Vol.69 (3), p.644-656</ispartof><rights>1991 American Heart Association, Inc.</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5400-7097f6606880221613f2ceabc4431ef7d7ea8a869e895f3b43ffd0f675c67623</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4991856$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1651816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, You-Qiu</creatorcontrib><creatorcontrib>Pickoff, Arthur S</creatorcontrib><creatorcontrib>Clarkson, Craig W</creatorcontrib><title>Evidence for Developmental Changes in Sodium Channel Inactivation Gating and Sodium Channel Block by Phenytoin in Rat Cardiac Myocytes</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>The voltage-dependent properties of the voltage-activated sodium channel were studied in neonatal (1–2-day-old) and adult rat ventricular cardiac myocytes using the whole-cell variation of the patch-clamp technique (16°C, [Na]i=15 mM, [Na]o=25 mM). The voltage dependence of the sodium conductance-membrane potential relation was similar in both neonatal and adult myocytes except for a difference in slope; the adult sodium conductance-membrane potential relation was slightly more steep. Neonatal cells also differed from adult cells by demonstrating a more negative voltage midpoint of their sodium availability curve, a slower rate of recovery from inactivation at hyperpolarized potentials, and a greater extent of slow inactivation development compared with adult cells. Phenytoin (40 μM) reduced the sodium current in a tonic and use-dependent manner in both adult and neonatal myocytes. However, phenytoin (40 μM) produced significantly more tonic block at negative holding potentials (e.g., −140 mV) in neonatal myocytes (22±5% [mean±SEMI, n=14) than in adult myocytes (10±2%, n=11) (p<0.05). The amplitudes of use-dependent block obtained during trains of 1-second pulses to −20 mV were also significantly greater in neonatal myocytes than in adult myocytes when the diastolic interval was varied over a range of 0.1–1.5 seconds (p<0.05). Definition of the time courses of block development at −20 mV indicated that phenytoin had a slightly higher affinity for inactivated sodium channels in neonatal cells. In addition, the time constant of recovery from use-dependent block by phenytoin was found to be significantly longer in neonatal cells than in adult cells at membrane potentials between −160 and −100 mV (p<0.001). The marked differences in phenytoin effect on cardiac sodium channels in neonatal versus adult rat cardiac myocytes suggest that there may be significant developmental changes in the sodium channel blocking effects of class I antiarrhythmic drugs in cardiac tissue. (Circulation Research 1991;69:644–656)</description><subject>Age Factors</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Biological and medical sciences</subject><subject>cardiac muscle</subject><subject>Cells, Cultured</subject><subject>channels</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gating</subject><subject>Heart</subject><subject>Heart - drug effects</subject><subject>Heart - physiology</subject><subject>inactivation</subject><subject>Membrane Potentials</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>phenytoin</subject><subject>Phenytoin - pharmacology</subject><subject>Rats</subject><subject>sodium</subject><subject>Sodium - metabolism</subject><subject>Sodium Channels - drug effects</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhiMEKtvCmROSD4hb0nHsOPERlqVUKgK1vVteZ9wN9dqLnWyVF-C567IrkLggzWg0M9_80ugvijcUKkoFPQdaRUyVkBWrBOfPigVtal7ypqXPiwUAyLJlDF4Wpyn9AKCc1fKkOKGioR0Vi-LXaj_06A0SGyL5hHt0YbdFP2pHlhvt7zCRwZOb0A_T9vfEoyOXXptx2OtxCJ5c5OLviPb9v9hHF8w9Wc_k-wb9PIYslONaj2SpYz9oQ77OwcwjplfFC6tdwtfHelbcfl7dLr-UV98uLpcfrkrTcICyBdlaIUB0HdR1_p_Z2qBeG84ZRdv2LepOd0JiJxvL1pxZ24MVbWNEK2p2Vrw_yO5i-DlhGtV2SAad0x7DlFRbA6-z8n9BKmouGiYzeH4ATQwpRbRqF4etjrOioJ4cUkDV9epGCamYyg7li7dH6Wm9xf4vf7Ak798d9zoZ7WzU3gzpD8alpF3zhPED9hDciDHdu-kBo9qgduNGZeOBAa1LmnGQuStzUmCP3zKotg</recordid><startdate>199109</startdate><enddate>199109</enddate><creator>Xu, You-Qiu</creator><creator>Pickoff, Arthur S</creator><creator>Clarkson, Craig W</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</scope><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>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>199109</creationdate><title>Evidence for Developmental Changes in Sodium Channel Inactivation Gating and Sodium Channel Block by Phenytoin in Rat Cardiac Myocytes</title><author>Xu, You-Qiu ; Pickoff, Arthur S ; Clarkson, Craig W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5400-7097f6606880221613f2ceabc4431ef7d7ea8a869e895f3b43ffd0f675c67623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Age Factors</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Biological and medical sciences</topic><topic>cardiac muscle</topic><topic>Cells, Cultured</topic><topic>channels</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gating</topic><topic>Heart</topic><topic>Heart - drug effects</topic><topic>Heart - physiology</topic><topic>inactivation</topic><topic>Membrane Potentials</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>phenytoin</topic><topic>Phenytoin - pharmacology</topic><topic>Rats</topic><topic>sodium</topic><topic>Sodium - metabolism</topic><topic>Sodium Channels - drug effects</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, You-Qiu</creatorcontrib><creatorcontrib>Pickoff, Arthur S</creatorcontrib><creatorcontrib>Clarkson, Craig W</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, You-Qiu</au><au>Pickoff, Arthur S</au><au>Clarkson, Craig W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence for Developmental Changes in Sodium Channel Inactivation Gating and Sodium Channel Block by Phenytoin in Rat Cardiac Myocytes</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>1991-09</date><risdate>1991</risdate><volume>69</volume><issue>3</issue><spage>644</spage><epage>656</epage><pages>644-656</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>The voltage-dependent properties of the voltage-activated sodium channel were studied in neonatal (1–2-day-old) and adult rat ventricular cardiac myocytes using the whole-cell variation of the patch-clamp technique (16°C, [Na]i=15 mM, [Na]o=25 mM). The voltage dependence of the sodium conductance-membrane potential relation was similar in both neonatal and adult myocytes except for a difference in slope; the adult sodium conductance-membrane potential relation was slightly more steep. Neonatal cells also differed from adult cells by demonstrating a more negative voltage midpoint of their sodium availability curve, a slower rate of recovery from inactivation at hyperpolarized potentials, and a greater extent of slow inactivation development compared with adult cells. Phenytoin (40 μM) reduced the sodium current in a tonic and use-dependent manner in both adult and neonatal myocytes. However, phenytoin (40 μM) produced significantly more tonic block at negative holding potentials (e.g., −140 mV) in neonatal myocytes (22±5% [mean±SEMI, n=14) than in adult myocytes (10±2%, n=11) (p<0.05). The amplitudes of use-dependent block obtained during trains of 1-second pulses to −20 mV were also significantly greater in neonatal myocytes than in adult myocytes when the diastolic interval was varied over a range of 0.1–1.5 seconds (p<0.05). Definition of the time courses of block development at −20 mV indicated that phenytoin had a slightly higher affinity for inactivated sodium channels in neonatal cells. In addition, the time constant of recovery from use-dependent block by phenytoin was found to be significantly longer in neonatal cells than in adult cells at membrane potentials between −160 and −100 mV (p<0.001). The marked differences in phenytoin effect on cardiac sodium channels in neonatal versus adult rat cardiac myocytes suggest that there may be significant developmental changes in the sodium channel blocking effects of class I antiarrhythmic drugs in cardiac tissue. (Circulation Research 1991;69:644–656)</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>1651816</pmid><doi>10.1161/01.res.69.3.644</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Age Factors Animals Animals, Newborn Biological and medical sciences cardiac muscle Cells, Cultured channels Fundamental and applied biological sciences. Psychology gating Heart Heart - drug effects Heart - physiology inactivation Membrane Potentials Myocardium - cytology Myocardium - metabolism phenytoin Phenytoin - pharmacology Rats sodium Sodium - metabolism Sodium Channels - drug effects Vertebrates: cardiovascular system |
| title | Evidence for Developmental Changes in Sodium Channel Inactivation Gating and Sodium Channel Block by Phenytoin in Rat Cardiac Myocytes |
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