Linked Life Data

9667364

Source:http://linkedlifedata.com/resource/pubmed/id/9667364

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pubmed-article:9667364pubmed:abstractTextAlthough a strong clinical association exists between congenital heart block (CHB) and an immune response to SSA/Ro and SSB/La proteins, a causative role of these antibodies in the pathogenesis is just emerging. In a preliminary report, we have demonstrated that IgG fractions isolated from the sera of mothers whose children have CHB are arrhythmogenic in the human fetal heart. To more precisely define the arrhythmogenic effect of anti-SSA/Ro-SSB/La antibodies, we used the readily available rat heart model to record: 1) ECGs from Langendorff beating hearts; 2) action potentials from atrioventricular (AV) nodal preparations; 3) L-type Ca currents, I(Ca) at the whole-cell and single channel levels; and 4) other currents such as the transient outward K+ current, I(to), the inward rectifier K+ current, I(K1), and the Na+ current, I(Na). Perfusion of hearts with purified IgG (800 microg/mL), isolated from the serum of a mother with SSA/Ro and SSB/La antibodies whose child had CHB, resulted in bradycardia associated with 2:1 AV block. Simultaneous action potentials were recorded from dissected atrial and AV nodal areas of the rat heart. Superfusion of these preparations with the same mother's IgG fraction resulted in 2:1 AV block followed by complete inhibition of AV nodal action potential. Because AV nodal electrogenesis is largely dependent on I(Ca), the effect of these antibodies on I(Ca) was subsequently determined. Superfusion of myocytes with whole serum or purified IgG (80 microg/mL) from the same mother consistently inhibited whole cell I(Ca), ensemble average Ba2+ currents (I(Ba)) and open state probability, p(o), without affecting the channel conductance. IgG had no significant effect on I(to), I(K1), or I(Na). Whole sera and IgG fractions from a healthy mother with no detectable anti-SSA/Ro or SSB/La antibodies did not inhibit I(Ca) or I(Ba). These results demonstrate that IgG containing anti-SSA/Ro and -SSB/La antibodies induces complete AV block in beating hearts and in multicellular preparations, thus implicating a preferential interaction of these autoantibodies with Ca channels and/or associated regulatory proteins. This is consistent with the observed inhibition of Ca channels that may be a critical factor contributing to the pathogenesis of CHB.lld:pubmed
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pubmed-article:9667364pubmed:authorpubmed-author:BuyonJ PJPlld:pubmed
pubmed-article:9667364pubmed:authorpubmed-author:ZhangZ HZHlld:pubmed
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pubmed-article:9667364pubmed:authorpubmed-author:TsengC ECElld:pubmed
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pubmed-article:9667364pubmed:pagination11-9lld:pubmed
pubmed-article:9667364pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:9667364pubmed:year1998lld:pubmed
pubmed-article:9667364pubmed:articleTitleSerum and immunoglobulin G from the mother of a child with congenital heart block induce conduction abnormalities and inhibit L-type calcium channels in a rat heart model.lld:pubmed
pubmed-article:9667364pubmed:affiliationDivision of Cardiology, Veterans Administration Medical Center and Center for Cardiovascular and Muscular Research, State University of New York, Brooklyn 11209, USA.lld:pubmed
pubmed-article:9667364pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:9667364pubmed:publicationTypeIn Vitrolld:pubmed
pubmed-article:9667364pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:9667364pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
pubmed-article:9667364pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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