Molecular Architecture of the Human Sinus Node : Insights Into the Function of the Cardiac Pacemaker
Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity. Quantitative polymerase c...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2009-03, Vol.119 (12), p.1562-1575 |
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| creator | CHANDLER, Natalie J GREENER, Ian D BILLETER, Rudolf SHARMA, Vinod SIGG, Daniel C BOYETT, Mark R DOBRZYNSKI, Halina TELLEZ, James O INADA, Shin MUSA, Hanny MOLENAAR, Peter DIFRANCESCO, Dario BARUSCOTTI, Mirko LONGHI, Renato ANDERSON, Robert H |
| description | Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity.
Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking.
Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking. |
| doi_str_mv | 10.1161/CIRCULATIONAHA.108.804369 |
| format | Article |
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Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking.
Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.108.804369</identifier><identifier>PMID: 19289639</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Biological and medical sciences ; Blood and lymphatic vessels ; Blood. Blood coagulation. Reticuloendothelial system ; Cardiac Electrophysiology ; Cardiology. Vascular system ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Heart Atria - chemistry ; Heart Conduction System - physiology ; Humans ; Ion Channels - analysis ; Ion Channels - genetics ; Ion Channels - physiology ; Medical sciences ; Models, Cardiovascular ; Myocardium - chemistry ; Pharmacology. Drug treatments ; RNA, Messenger - analysis ; Sinoatrial Node - chemistry ; Sinoatrial Node - physiology ; Tissue Distribution</subject><ispartof>Circulation (New York, N.Y.), 2009-03, Vol.119 (12), p.1562-1575</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-a7985df29994fad39673219a578634b0931377d59cdee7a50ac71be85e727c723</citedby><cites>FETCH-LOGICAL-c388t-a7985df29994fad39673219a578634b0931377d59cdee7a50ac71be85e727c723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21374584$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19289639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHANDLER, Natalie J</creatorcontrib><creatorcontrib>GREENER, Ian D</creatorcontrib><creatorcontrib>BILLETER, Rudolf</creatorcontrib><creatorcontrib>SHARMA, Vinod</creatorcontrib><creatorcontrib>SIGG, Daniel C</creatorcontrib><creatorcontrib>BOYETT, Mark R</creatorcontrib><creatorcontrib>DOBRZYNSKI, Halina</creatorcontrib><creatorcontrib>TELLEZ, James O</creatorcontrib><creatorcontrib>INADA, Shin</creatorcontrib><creatorcontrib>MUSA, Hanny</creatorcontrib><creatorcontrib>MOLENAAR, Peter</creatorcontrib><creatorcontrib>DIFRANCESCO, Dario</creatorcontrib><creatorcontrib>BARUSCOTTI, Mirko</creatorcontrib><creatorcontrib>LONGHI, Renato</creatorcontrib><creatorcontrib>ANDERSON, Robert H</creatorcontrib><title>Molecular Architecture of the Human Sinus Node : Insights Into the Function of the Cardiac Pacemaker</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity.
Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking.
Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.</description><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cardiac Electrophysiology</subject><subject>Cardiology. Vascular system</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Heart Atria - chemistry</subject><subject>Heart Conduction System - physiology</subject><subject>Humans</subject><subject>Ion Channels - analysis</subject><subject>Ion Channels - genetics</subject><subject>Ion Channels - physiology</subject><subject>Medical sciences</subject><subject>Models, Cardiovascular</subject><subject>Myocardium - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>RNA, Messenger - analysis</subject><subject>Sinoatrial Node - chemistry</subject><subject>Sinoatrial Node - physiology</subject><subject>Tissue Distribution</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkF1P2zAUhq2Jae3K_sJkLuAuxY7j2N5dFMFaqbQTa6-jU-dkDeQD7OSCf4-hZdOuzoee93y8hFxwNuc85df58j7frbLtcrPOFtmcMz3XLBGp-USmXMZJlEhhzsiUMWYiJeJ4Qr56_xDKVCj5hUy4ibVJhZmS8q5v0I4NOJo5e6gHtMPokPYVHQ5IF2MLHf1dd6On675E-oMuO1__OQw-JEP_Dt2OnR3qvvsQ5eDKGiz9BRZbeER3Tj5X0Hj8doozsru92eaLaLX5ucyzVWSF1kMEymhZVrExJqmgFCYNt3MDUulUJHtmBBdKldLYElGBZGAV36OWqGJlVSxm5Oo498n1zyP6oWhrb7FpoMN-9EWqmDZaJwE0R9C63nuHVfHk6hbcS8FZ8WZx8b_Foa2Lo8VB-_20ZNy3WP5TnjwNwOUJAG-hqRx0tvZ_uTg8kchwxCvul4VO</recordid><startdate>20090331</startdate><enddate>20090331</enddate><creator>CHANDLER, Natalie J</creator><creator>GREENER, Ian D</creator><creator>BILLETER, Rudolf</creator><creator>SHARMA, Vinod</creator><creator>SIGG, Daniel C</creator><creator>BOYETT, Mark R</creator><creator>DOBRZYNSKI, Halina</creator><creator>TELLEZ, James O</creator><creator>INADA, Shin</creator><creator>MUSA, Hanny</creator><creator>MOLENAAR, Peter</creator><creator>DIFRANCESCO, Dario</creator><creator>BARUSCOTTI, Mirko</creator><creator>LONGHI, Renato</creator><creator>ANDERSON, Robert H</creator><general>Lippincott Williams & Wilkins</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>20090331</creationdate><title>Molecular Architecture of the Human Sinus Node : Insights Into the Function of the Cardiac Pacemaker</title><author>CHANDLER, Natalie J ; GREENER, Ian D ; BILLETER, Rudolf ; SHARMA, Vinod ; SIGG, Daniel C ; BOYETT, Mark R ; DOBRZYNSKI, Halina ; TELLEZ, James O ; INADA, Shin ; MUSA, Hanny ; MOLENAAR, Peter ; DIFRANCESCO, Dario ; BARUSCOTTI, Mirko ; LONGHI, Renato ; ANDERSON, Robert H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-a7985df29994fad39673219a578634b0931377d59cdee7a50ac71be85e727c723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood. 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Drug treatments</topic><topic>RNA, Messenger - analysis</topic><topic>Sinoatrial Node - chemistry</topic><topic>Sinoatrial Node - physiology</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHANDLER, Natalie J</creatorcontrib><creatorcontrib>GREENER, Ian D</creatorcontrib><creatorcontrib>BILLETER, Rudolf</creatorcontrib><creatorcontrib>SHARMA, Vinod</creatorcontrib><creatorcontrib>SIGG, Daniel C</creatorcontrib><creatorcontrib>BOYETT, Mark R</creatorcontrib><creatorcontrib>DOBRZYNSKI, Halina</creatorcontrib><creatorcontrib>TELLEZ, James O</creatorcontrib><creatorcontrib>INADA, Shin</creatorcontrib><creatorcontrib>MUSA, Hanny</creatorcontrib><creatorcontrib>MOLENAAR, Peter</creatorcontrib><creatorcontrib>DIFRANCESCO, Dario</creatorcontrib><creatorcontrib>BARUSCOTTI, Mirko</creatorcontrib><creatorcontrib>LONGHI, Renato</creatorcontrib><creatorcontrib>ANDERSON, Robert H</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>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHANDLER, Natalie J</au><au>GREENER, Ian D</au><au>BILLETER, Rudolf</au><au>SHARMA, Vinod</au><au>SIGG, Daniel C</au><au>BOYETT, Mark R</au><au>DOBRZYNSKI, Halina</au><au>TELLEZ, James O</au><au>INADA, Shin</au><au>MUSA, Hanny</au><au>MOLENAAR, Peter</au><au>DIFRANCESCO, Dario</au><au>BARUSCOTTI, Mirko</au><au>LONGHI, Renato</au><au>ANDERSON, Robert H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Architecture of the Human Sinus Node : Insights Into the Function of the Cardiac Pacemaker</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2009-03-31</date><risdate>2009</risdate><volume>119</volume><issue>12</issue><spage>1562</spage><epage>1575</epage><pages>1562-1575</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity.
Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking.
Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>19289639</pmid><doi>10.1161/CIRCULATIONAHA.108.804369</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biological and medical sciences Blood and lymphatic vessels Blood. Blood coagulation. Reticuloendothelial system Cardiac Electrophysiology Cardiology. Vascular system Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Heart Atria - chemistry Heart Conduction System - physiology Humans Ion Channels - analysis Ion Channels - genetics Ion Channels - physiology Medical sciences Models, Cardiovascular Myocardium - chemistry Pharmacology. Drug treatments RNA, Messenger - analysis Sinoatrial Node - chemistry Sinoatrial Node - physiology Tissue Distribution |
| title | Molecular Architecture of the Human Sinus Node : Insights Into the Function of the Cardiac Pacemaker |
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