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Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation
The rapid atrial rate during atrial fibrillation (AF) decreases the ionic current density of transient outward K+ current, L-type Ca2+ current, and Na+ current, thereby altering cardiac electrophysiology and promoting arrhythmia maintenance. To assess possible underlying changes in cardiac gene expr...
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| Published in: | Circulation research 1999-04, Vol.84 (7), p.776-784 |
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| Main Authors: | , , , , |
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| cites | cdi_FETCH-LOGICAL-c538t-a0aed898afbc622de7c23f90af6804f194d728617746221b19641156bdab10f33 |
| container_end_page | 784 |
| container_issue | 7 |
| container_start_page | 776 |
| container_title | Circulation research |
| container_volume | 84 |
| creator | LIXIA YUE MELNYK, P GASPO, R ZHIGUO WANG NATTEL, S |
| description | The rapid atrial rate during atrial fibrillation (AF) decreases the ionic current density of transient outward K+ current, L-type Ca2+ current, and Na+ current, thereby altering cardiac electrophysiology and promoting arrhythmia maintenance. To assess possible underlying changes in cardiac gene expression, we applied competitive reverse transcriptase-polymerase chain reaction to quantify mRNA concentrations in dogs subjected to 7 (group P7 dogs) or 42 (group P42 dogs) days of atrial pacing at 400 bpm and in sham controls. Rapid pacing reduced mRNA concentrations of Kv4.3 (putative gene encoding transient outward K+ current; by 60% in P7 and 74% in P42 dogs; P |
| doi_str_mv | 10.1161/01.res.84.7.776 |
| format | article |
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To assess possible underlying changes in cardiac gene expression, we applied competitive reverse transcriptase-polymerase chain reaction to quantify mRNA concentrations in dogs subjected to 7 (group P7 dogs) or 42 (group P42 dogs) days of atrial pacing at 400 bpm and in sham controls. Rapid pacing reduced mRNA concentrations of Kv4.3 (putative gene encoding transient outward K+ current; by 60% in P7 and 74% in P42 dogs; P<0.01 and P<0.001, respectively, versus shams), the alpha1c subunit of L-type Ca2+ channels (by 57% in P7 and 72% in P42 dogs; P<0.01 versus shams for each) and the alpha subunit of cardiac Na+ channels (by 18% in P7 and 42% in P42; P=NS and P<0.01, respectively, versus shams) genes. The observed changes in ion channel mRNA concentrations paralleled previously measured changes in corresponding atrial ionic current densities. Atrial tachycardia did not affect mRNA concentrations of genes encoding delayed or Kir2.1 inward rectifier K+ currents (of which the densities are unchanged by atrial tachycardia) or of the Na+,Ca2+ exchanger. Western blot techniques were used to quantify protein expression for Kv4.3 and Na+ channel alpha subunits, which were decreased by 72% and 47%, respectively, in P42 dogs (P<0.001 versus control for each), in a manner quantitatively similar to measured changes in mRNA and currents, whereas Na+,Ca2+ exchanger protein concentration was unchanged. We conclude that chronic atrial tachycardia alters atrial ion channel gene expression, thereby altering ionic currents in a fashion that promotes the occurrence of AF. These observations provide a potential molecular basis for the self-perpetuating nature of AF.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.res.84.7.776</identifier><identifier>PMID: 10205145</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Animals ; Antisense Elements (Genetics) ; Atrial Fibrillation - physiopathology ; Biological and medical sciences ; Blotting, Western ; Calcium Channels - analysis ; Calcium Channels - genetics ; Calcium Channels, L-Type ; Cardiac dysrhythmias ; Cardiology. Vascular system ; Cloning, Molecular ; Disease Models, Animal ; DNA, Complementary ; Dogs ; Gene Expression - physiology ; Heart ; Medical sciences ; Myocardium - chemistry ; Potassium Channels - analysis ; Potassium Channels - genetics ; Potassium Channels, Inwardly Rectifying ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Sodium Channels - analysis ; Sodium Channels - genetics ; Transcription, Genetic - physiology</subject><ispartof>Circulation research, 1999-04, Vol.84 (7), p.776-784</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Apr 16, 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-a0aed898afbc622de7c23f90af6804f194d728617746221b19641156bdab10f33</citedby><cites>FETCH-LOGICAL-c538t-a0aed898afbc622de7c23f90af6804f194d728617746221b19641156bdab10f33</cites></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=1787361$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10205145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LIXIA YUE</creatorcontrib><creatorcontrib>MELNYK, P</creatorcontrib><creatorcontrib>GASPO, R</creatorcontrib><creatorcontrib>ZHIGUO WANG</creatorcontrib><creatorcontrib>NATTEL, S</creatorcontrib><title>Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>The rapid atrial rate during atrial fibrillation (AF) decreases the ionic current density of transient outward K+ current, L-type Ca2+ current, and Na+ current, thereby altering cardiac electrophysiology and promoting arrhythmia maintenance. To assess possible underlying changes in cardiac gene expression, we applied competitive reverse transcriptase-polymerase chain reaction to quantify mRNA concentrations in dogs subjected to 7 (group P7 dogs) or 42 (group P42 dogs) days of atrial pacing at 400 bpm and in sham controls. Rapid pacing reduced mRNA concentrations of Kv4.3 (putative gene encoding transient outward K+ current; by 60% in P7 and 74% in P42 dogs; P<0.01 and P<0.001, respectively, versus shams), the alpha1c subunit of L-type Ca2+ channels (by 57% in P7 and 72% in P42 dogs; P<0.01 versus shams for each) and the alpha subunit of cardiac Na+ channels (by 18% in P7 and 42% in P42; P=NS and P<0.01, respectively, versus shams) genes. The observed changes in ion channel mRNA concentrations paralleled previously measured changes in corresponding atrial ionic current densities. Atrial tachycardia did not affect mRNA concentrations of genes encoding delayed or Kir2.1 inward rectifier K+ currents (of which the densities are unchanged by atrial tachycardia) or of the Na+,Ca2+ exchanger. Western blot techniques were used to quantify protein expression for Kv4.3 and Na+ channel alpha subunits, which were decreased by 72% and 47%, respectively, in P42 dogs (P<0.001 versus control for each), in a manner quantitatively similar to measured changes in mRNA and currents, whereas Na+,Ca2+ exchanger protein concentration was unchanged. We conclude that chronic atrial tachycardia alters atrial ion channel gene expression, thereby altering ionic currents in a fashion that promotes the occurrence of AF. These observations provide a potential molecular basis for the self-perpetuating nature of AF.</description><subject>Animals</subject><subject>Antisense Elements (Genetics)</subject><subject>Atrial Fibrillation - physiopathology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Calcium Channels - analysis</subject><subject>Calcium Channels - genetics</subject><subject>Calcium Channels, L-Type</subject><subject>Cardiac dysrhythmias</subject><subject>Cardiology. Vascular system</subject><subject>Cloning, Molecular</subject><subject>Disease Models, Animal</subject><subject>DNA, Complementary</subject><subject>Dogs</subject><subject>Gene Expression - physiology</subject><subject>Heart</subject><subject>Medical sciences</subject><subject>Myocardium - chemistry</subject><subject>Potassium Channels - analysis</subject><subject>Potassium Channels - genetics</subject><subject>Potassium Channels, Inwardly Rectifying</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Sodium Channels - analysis</subject><subject>Sodium Channels - genetics</subject><subject>Transcription, Genetic - physiology</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNpdkM1r3DAUxEVp6W4-zr0FUUpudvQkWbKOIaRJYUMhX1chy1KqRbY20vqQ_z5OdiElpwfzfjMMg9APIDWAgDMCdXalbnktaynFF7SEhvKKNxK-oiUhRFWSMbJAB6WsCQHOqPqOFkAoaYA3S_R4k6KzUzQZD87-M2MoQ8HT2LscX8L4hEMag8XZDal38V0YscF9esLvCk4em20OJmIfuhxiNNvZcoS-eROLO97fQ_Tw-_L-4rpa_b36c3G-qmzD2m1liHF9q1rjOyso7Z20lHlFjBct4R4U7yVtBUjJ5zd0oAQHaETXmw6IZ-wQne5yNzk9T65s9RCKdXOL0aWpaKGEUhKaGfz5CVynKY9zN02BchBSvUFnO8jmVEp2Xm9yGEx-0UD0296agL69vNMt11LPe8-Ok33s1A2u_4_fDTwDv_aAKdZEn81oQ_ngZCuZAPYKsAmHxA</recordid><startdate>19990416</startdate><enddate>19990416</enddate><creator>LIXIA YUE</creator><creator>MELNYK, P</creator><creator>GASPO, R</creator><creator>ZHIGUO WANG</creator><creator>NATTEL, S</creator><general>Lippincott</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>19990416</creationdate><title>Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation</title><author>LIXIA YUE ; MELNYK, P ; GASPO, R ; ZHIGUO WANG ; NATTEL, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-a0aed898afbc622de7c23f90af6804f194d728617746221b19641156bdab10f33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Antisense Elements (Genetics)</topic><topic>Atrial Fibrillation - physiopathology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Calcium Channels - analysis</topic><topic>Calcium Channels - genetics</topic><topic>Calcium Channels, L-Type</topic><topic>Cardiac dysrhythmias</topic><topic>Cardiology. Vascular system</topic><topic>Cloning, Molecular</topic><topic>Disease Models, Animal</topic><topic>DNA, Complementary</topic><topic>Dogs</topic><topic>Gene Expression - physiology</topic><topic>Heart</topic><topic>Medical sciences</topic><topic>Myocardium - chemistry</topic><topic>Potassium Channels - analysis</topic><topic>Potassium Channels - genetics</topic><topic>Potassium Channels, Inwardly Rectifying</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Sodium Channels - analysis</topic><topic>Sodium Channels - genetics</topic><topic>Transcription, Genetic - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LIXIA YUE</creatorcontrib><creatorcontrib>MELNYK, P</creatorcontrib><creatorcontrib>GASPO, R</creatorcontrib><creatorcontrib>ZHIGUO WANG</creatorcontrib><creatorcontrib>NATTEL, S</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>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LIXIA YUE</au><au>MELNYK, P</au><au>GASPO, R</au><au>ZHIGUO WANG</au><au>NATTEL, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>1999-04-16</date><risdate>1999</risdate><volume>84</volume><issue>7</issue><spage>776</spage><epage>784</epage><pages>776-784</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>The rapid atrial rate during atrial fibrillation (AF) decreases the ionic current density of transient outward K+ current, L-type Ca2+ current, and Na+ current, thereby altering cardiac electrophysiology and promoting arrhythmia maintenance. To assess possible underlying changes in cardiac gene expression, we applied competitive reverse transcriptase-polymerase chain reaction to quantify mRNA concentrations in dogs subjected to 7 (group P7 dogs) or 42 (group P42 dogs) days of atrial pacing at 400 bpm and in sham controls. Rapid pacing reduced mRNA concentrations of Kv4.3 (putative gene encoding transient outward K+ current; by 60% in P7 and 74% in P42 dogs; P<0.01 and P<0.001, respectively, versus shams), the alpha1c subunit of L-type Ca2+ channels (by 57% in P7 and 72% in P42 dogs; P<0.01 versus shams for each) and the alpha subunit of cardiac Na+ channels (by 18% in P7 and 42% in P42; P=NS and P<0.01, respectively, versus shams) genes. The observed changes in ion channel mRNA concentrations paralleled previously measured changes in corresponding atrial ionic current densities. Atrial tachycardia did not affect mRNA concentrations of genes encoding delayed or Kir2.1 inward rectifier K+ currents (of which the densities are unchanged by atrial tachycardia) or of the Na+,Ca2+ exchanger. Western blot techniques were used to quantify protein expression for Kv4.3 and Na+ channel alpha subunits, which were decreased by 72% and 47%, respectively, in P42 dogs (P<0.001 versus control for each), in a manner quantitatively similar to measured changes in mRNA and currents, whereas Na+,Ca2+ exchanger protein concentration was unchanged. We conclude that chronic atrial tachycardia alters atrial ion channel gene expression, thereby altering ionic currents in a fashion that promotes the occurrence of AF. These observations provide a potential molecular basis for the self-perpetuating nature of AF.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>10205145</pmid><doi>10.1161/01.res.84.7.776</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation research, 1999-04, Vol.84 (7), p.776-784 |
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| language | eng |
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| source | Freely Accessible Science Journals |
| subjects | Animals Antisense Elements (Genetics) Atrial Fibrillation - physiopathology Biological and medical sciences Blotting, Western Calcium Channels - analysis Calcium Channels - genetics Calcium Channels, L-Type Cardiac dysrhythmias Cardiology. Vascular system Cloning, Molecular Disease Models, Animal DNA, Complementary Dogs Gene Expression - physiology Heart Medical sciences Myocardium - chemistry Potassium Channels - analysis Potassium Channels - genetics Potassium Channels, Inwardly Rectifying Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Sodium Channels - analysis Sodium Channels - genetics Transcription, Genetic - physiology |
| title | Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation |
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