Source:http://linkedlifedata.com/resource/pubmed/id/14963005
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2004-3-5
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pubmed:abstractText |
Congenital heart block (CHB) is a conduction abnormality characterized by complete atrioventricular (AV) block. CHB affects fetuses and/or newborn of mothers with autoantibodies reactive with ribonucleoproteins 48-kDa SSB/La, 52-kDa SSA/Ro, and 60-kDa SSA/Ro. We recently established animal models of CHB and reported, for the first time, significant sinus bradycardia preceding AV block. This unexpected observation implies that the spectrum of conduction abnormalities extends beyond the AV node to also affect the SA node. To test this hypothesis, we investigated the functional basis of this sinus bradycardia by characterizing the effects of antibodies from mothers with CHB children (positive IgG) on ionic currents that are known to significantly contribute to spontaneous pacing in SA node cells. We recorded L- (I(Ca.L)) and T- (I(Ca.T)) type Ca2+, delayed rectifier K+ (I(K)), hyperpolarization-activated (I(f)) currents, and action potentials (APs) from young rabbit SA node cells. We demonstrated that positive IgG significantly inhibited both I(Ca.T) and I(Ca.L) and induced sinus bradycardia but did not affect I(f) and I(K). Normal IgG from mothers with healthy children did not affect all the currents studied and APs. These results establish that IgG from mothers with CHB children causes substantial inhibition of I(Ca.T) and I(Ca.L), two important pacemaker currents in rabbit SA node cells and point to both I(Ca.T) and I(Ca.L) as major players in the ionic mechanism by which maternal antibodies induce sinus bradycardia in CHB. These novel findings have important clinical significance and suggest that sinus bradycardia may be a potential marker in the detection and prevention of CHB. The full text of this article is available online at http://circres.ahajournals.org
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Antinuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantigens,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, L-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, T-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Cytoplasmic,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/SS-A antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/SS-A antigen,
http://linkedlifedata.com/resource/pubmed/chemical/SS-B antigen,
http://linkedlifedata.com/resource/pubmed/chemical/TROVE2 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1524-4571
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
5
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pubmed:volume |
94
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e32-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:14963005-Action Potentials,
pubmed-meshheading:14963005-Adult,
pubmed-meshheading:14963005-Animals,
pubmed-meshheading:14963005-Antibodies, Antinuclear,
pubmed-meshheading:14963005-Arrhythmia, Sinus,
pubmed-meshheading:14963005-Autoantigens,
pubmed-meshheading:14963005-Bradycardia,
pubmed-meshheading:14963005-Calcium,
pubmed-meshheading:14963005-Calcium Channels, L-Type,
pubmed-meshheading:14963005-Calcium Channels, T-Type,
pubmed-meshheading:14963005-Female,
pubmed-meshheading:14963005-Heart Block,
pubmed-meshheading:14963005-Humans,
pubmed-meshheading:14963005-Immunity, Maternally-Acquired,
pubmed-meshheading:14963005-Immunoglobulin G,
pubmed-meshheading:14963005-Ion Transport,
pubmed-meshheading:14963005-Pregnancy,
pubmed-meshheading:14963005-RNA, Small Cytoplasmic,
pubmed-meshheading:14963005-Rabbits,
pubmed-meshheading:14963005-Ribonucleoproteins,
pubmed-meshheading:14963005-Sinoatrial Node
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pubmed:year |
2004
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pubmed:articleTitle |
Functional basis of sinus bradycardia in congenital heart block.
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pubmed:affiliation |
Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, SUNY Downstate Medical Center and NYU School of Medicine, Brooklyn, NY 11209, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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