Conduction slowing by the gap junctional uncoupler carbenoxolone
Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythmias. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of carbenoxolone on c...
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| Veröffentlicht in: | Cardiovascular research 2003-11, Vol.60 (2), p.288-297 |
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| creator | DE GROOT, Joris R VEENSTRA, Thijs VERHEIJCK, E. Etienne VERKERK, Arie O WILDERS, Ronald SMITS, Jeroen P. P WILMS-SCHOPMAN, Francien J. G WIEGERINCK, Rob F BOURIER, Jan BELTERMAN, Charly N. W CORONEL, Ruben |
| description | Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythmias. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of carbenoxolone on cellular electrical coupling, membrane ionic currents, and atrial and ventricular conduction.
In isolated rabbit left ventricular and right atrial myocytes, carbenoxolone (50 micromol/l) had no effect on action potential characteristics. Calcium, potassium, and sodium currents remained unchanged. Dual current clamp experiments on poorly coupled cell pairs revealed a 21+/-3% decrease in coupling conductance by carbenoxolone (mean+/-S.E.M., n=4, p |
| doi_str_mv | 10.1016/j.cardiores.2003.07.004 |
| format | Article |
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In isolated rabbit left ventricular and right atrial myocytes, carbenoxolone (50 micromol/l) had no effect on action potential characteristics. Calcium, potassium, and sodium currents remained unchanged. Dual current clamp experiments on poorly coupled cell pairs revealed a 21+/-3% decrease in coupling conductance by carbenoxolone (mean+/-S.E.M., n=4, p<0.05). High-density activation mapping was performed in intact rabbit atrium and ventricle during Langendorff perfusion of the heart. The amplitude of the Laplacian of the electrograms, a measure of coupling current in intact hearts, decreased from 1.45+/-0.66 to 0.75+/-0.51 microA/mm(3) (mean+/-SD, n=32, p<0.05) after 15 min of carbenoxolone. Carbenoxolone reversibly decreased longitudinal and transversal conduction velocity from 66+/-15 to 49+/-16 cm/s and from 50+/-14 to 35+/-15 cm/s in ventricle, respectively (mean+/-SD, n=5, both p<0.05). In atrium, longitudinal and transversal conduction velocity decreased from 80+/-29 to 60+/-16 cm/s and from 49+/-10 to 38+/-10 cm/s (mean+/-SD, n=8, both p<0.05).
Carbenoxolone-induced uncoupling causes atrial and ventricular conduction slowing without affecting cardiac membrane currents. Activation delay is larger in poorly coupled cells.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1016/j.cardiores.2003.07.004</identifier><identifier>PMID: 14613858</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Action Potentials - drug effects ; Animals ; Biological and medical sciences ; Carbenoxolone - pharmacology ; Cell Separation - methods ; Cells, Cultured ; Drug toxicity and drugs side effects treatment ; Female ; Gap Junctions - drug effects ; Heart Conduction System - drug effects ; Ion Channels - genetics ; Male ; Medical sciences ; Perfusion ; Pharmacology. Drug treatments ; Rabbits ; Toxicity: cardiovascular system ; Uncoupling Agents - pharmacology</subject><ispartof>Cardiovascular research, 2003-11, Vol.60 (2), p.288-297</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-7c772b6464bcbf6faff3d3ff56d8ab7107f9563e74f4e3214cfa8f840a54829f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15209688$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14613858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DE GROOT, Joris R</creatorcontrib><creatorcontrib>VEENSTRA, Thijs</creatorcontrib><creatorcontrib>VERHEIJCK, E. Etienne</creatorcontrib><creatorcontrib>VERKERK, Arie O</creatorcontrib><creatorcontrib>WILDERS, Ronald</creatorcontrib><creatorcontrib>SMITS, Jeroen P. P</creatorcontrib><creatorcontrib>WILMS-SCHOPMAN, Francien J. G</creatorcontrib><creatorcontrib>WIEGERINCK, Rob F</creatorcontrib><creatorcontrib>BOURIER, Jan</creatorcontrib><creatorcontrib>BELTERMAN, Charly N. W</creatorcontrib><creatorcontrib>CORONEL, Ruben</creatorcontrib><title>Conduction slowing by the gap junctional uncoupler carbenoxolone</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythmias. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of carbenoxolone on cellular electrical coupling, membrane ionic currents, and atrial and ventricular conduction.
In isolated rabbit left ventricular and right atrial myocytes, carbenoxolone (50 micromol/l) had no effect on action potential characteristics. Calcium, potassium, and sodium currents remained unchanged. Dual current clamp experiments on poorly coupled cell pairs revealed a 21+/-3% decrease in coupling conductance by carbenoxolone (mean+/-S.E.M., n=4, p<0.05). High-density activation mapping was performed in intact rabbit atrium and ventricle during Langendorff perfusion of the heart. The amplitude of the Laplacian of the electrograms, a measure of coupling current in intact hearts, decreased from 1.45+/-0.66 to 0.75+/-0.51 microA/mm(3) (mean+/-SD, n=32, p<0.05) after 15 min of carbenoxolone. Carbenoxolone reversibly decreased longitudinal and transversal conduction velocity from 66+/-15 to 49+/-16 cm/s and from 50+/-14 to 35+/-15 cm/s in ventricle, respectively (mean+/-SD, n=5, both p<0.05). In atrium, longitudinal and transversal conduction velocity decreased from 80+/-29 to 60+/-16 cm/s and from 49+/-10 to 38+/-10 cm/s (mean+/-SD, n=8, both p<0.05).
Carbenoxolone-induced uncoupling causes atrial and ventricular conduction slowing without affecting cardiac membrane currents. Activation delay is larger in poorly coupled cells.</description><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carbenoxolone - pharmacology</subject><subject>Cell Separation - methods</subject><subject>Cells, Cultured</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Female</subject><subject>Gap Junctions - drug effects</subject><subject>Heart Conduction System - drug effects</subject><subject>Ion Channels - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Perfusion</subject><subject>Pharmacology. Drug treatments</subject><subject>Rabbits</subject><subject>Toxicity: cardiovascular system</subject><subject>Uncoupling Agents - pharmacology</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtOwzAQRS0EoqXwC5AN7BLs-NkdqOIlVWIDa8tx7JLItYOdCPr3pDSC1cxozsyVDgBXCBYIInbbFlrFugnRpKKEEBeQFxCSIzBHnNIcl4QegzmEUOQMMzwDZym140gpJ6dghghDWFAxB3er4OtB903wWXLhq_GbrNpl_YfJNqrL2sH_7pTLxi4MnTMxG6Mr48N3cMGbc3BilUvmYqoL8P748LZ6ztevTy-r-3WuCWV9zjXnZcUII5WuLLPKWlxjaymrhao4gtwuKcOGE0sMLhHRVgkrCFSUiHJp8QLcHP52MXwOJvVy2yRtnFPehCFJjjDHtMQjyA-gjiGlaKzsYrNVcScRlHt5spV_8uRenoRcjvLGy8spYqi2pv6_m2yNwPUEqKSVs1F53aR_jpZwyYTAPzZ3fBM</recordid><startdate>20031101</startdate><enddate>20031101</enddate><creator>DE GROOT, Joris R</creator><creator>VEENSTRA, Thijs</creator><creator>VERHEIJCK, E. Etienne</creator><creator>VERKERK, Arie O</creator><creator>WILDERS, Ronald</creator><creator>SMITS, Jeroen P. P</creator><creator>WILMS-SCHOPMAN, Francien J. G</creator><creator>WIEGERINCK, Rob F</creator><creator>BOURIER, Jan</creator><creator>BELTERMAN, Charly N. W</creator><creator>CORONEL, Ruben</creator><general>Oxford University Press</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>7X8</scope></search><sort><creationdate>20031101</creationdate><title>Conduction slowing by the gap junctional uncoupler carbenoxolone</title><author>DE GROOT, Joris R ; VEENSTRA, Thijs ; VERHEIJCK, E. Etienne ; VERKERK, Arie O ; WILDERS, Ronald ; SMITS, Jeroen P. P ; WILMS-SCHOPMAN, Francien J. G ; WIEGERINCK, Rob F ; BOURIER, Jan ; BELTERMAN, Charly N. W ; CORONEL, Ruben</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-7c772b6464bcbf6faff3d3ff56d8ab7107f9563e74f4e3214cfa8f840a54829f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carbenoxolone - pharmacology</topic><topic>Cell Separation - methods</topic><topic>Cells, Cultured</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Female</topic><topic>Gap Junctions - drug effects</topic><topic>Heart Conduction System - drug effects</topic><topic>Ion Channels - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Perfusion</topic><topic>Pharmacology. Drug treatments</topic><topic>Rabbits</topic><topic>Toxicity: cardiovascular system</topic><topic>Uncoupling Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DE GROOT, Joris R</creatorcontrib><creatorcontrib>VEENSTRA, Thijs</creatorcontrib><creatorcontrib>VERHEIJCK, E. Etienne</creatorcontrib><creatorcontrib>VERKERK, Arie O</creatorcontrib><creatorcontrib>WILDERS, Ronald</creatorcontrib><creatorcontrib>SMITS, Jeroen P. P</creatorcontrib><creatorcontrib>WILMS-SCHOPMAN, Francien J. G</creatorcontrib><creatorcontrib>WIEGERINCK, Rob F</creatorcontrib><creatorcontrib>BOURIER, Jan</creatorcontrib><creatorcontrib>BELTERMAN, Charly N. W</creatorcontrib><creatorcontrib>CORONEL, Ruben</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>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DE GROOT, Joris R</au><au>VEENSTRA, Thijs</au><au>VERHEIJCK, E. Etienne</au><au>VERKERK, Arie O</au><au>WILDERS, Ronald</au><au>SMITS, Jeroen P. P</au><au>WILMS-SCHOPMAN, Francien J. G</au><au>WIEGERINCK, Rob F</au><au>BOURIER, Jan</au><au>BELTERMAN, Charly N. W</au><au>CORONEL, Ruben</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conduction slowing by the gap junctional uncoupler carbenoxolone</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2003-11-01</date><risdate>2003</risdate><volume>60</volume><issue>2</issue><spage>288</spage><epage>297</epage><pages>288-297</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythmias. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of carbenoxolone on cellular electrical coupling, membrane ionic currents, and atrial and ventricular conduction.
In isolated rabbit left ventricular and right atrial myocytes, carbenoxolone (50 micromol/l) had no effect on action potential characteristics. Calcium, potassium, and sodium currents remained unchanged. Dual current clamp experiments on poorly coupled cell pairs revealed a 21+/-3% decrease in coupling conductance by carbenoxolone (mean+/-S.E.M., n=4, p<0.05). High-density activation mapping was performed in intact rabbit atrium and ventricle during Langendorff perfusion of the heart. The amplitude of the Laplacian of the electrograms, a measure of coupling current in intact hearts, decreased from 1.45+/-0.66 to 0.75+/-0.51 microA/mm(3) (mean+/-SD, n=32, p<0.05) after 15 min of carbenoxolone. Carbenoxolone reversibly decreased longitudinal and transversal conduction velocity from 66+/-15 to 49+/-16 cm/s and from 50+/-14 to 35+/-15 cm/s in ventricle, respectively (mean+/-SD, n=5, both p<0.05). In atrium, longitudinal and transversal conduction velocity decreased from 80+/-29 to 60+/-16 cm/s and from 49+/-10 to 38+/-10 cm/s (mean+/-SD, n=8, both p<0.05).
Carbenoxolone-induced uncoupling causes atrial and ventricular conduction slowing without affecting cardiac membrane currents. Activation delay is larger in poorly coupled cells.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>14613858</pmid><doi>10.1016/j.cardiores.2003.07.004</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Action Potentials - drug effects Animals Biological and medical sciences Carbenoxolone - pharmacology Cell Separation - methods Cells, Cultured Drug toxicity and drugs side effects treatment Female Gap Junctions - drug effects Heart Conduction System - drug effects Ion Channels - genetics Male Medical sciences Perfusion Pharmacology. Drug treatments Rabbits Toxicity: cardiovascular system Uncoupling Agents - pharmacology |
| title | Conduction slowing by the gap junctional uncoupler carbenoxolone |
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