Source:http://linkedlifedata.com/resource/pubmed/id/11215536
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
|
pubmed:dateCreated |
2001-2-15
|
pubmed:abstractText |
Molecular and electrical remodeling of ion channels determining action potential duration has been proposed as a major mechanism in chronic atrial fibrillation. We investigated the mRNA expression of the cardiac L-type Ca2+-channel subunits alpha1c, alpha2/delta1, beta1a, and beta1b/c in atrial tissue of patients with chronic atrial fibrillation compared to patients in sinus rhythm. In addition, the mRNA expression of the 5-hydroxytryptamine type 4-, beta1-, and beta2-adrenergic receptors, which are known to stimulate the L-type Ca2+-current in human atrium, was analyzed and the effect of chronic beta-blocker treatment on the mRNA expression of these receptors and of the L-type Ca2+-channel subunits was assessed. Total RNA was isolated from right atrial appendages of patients in sinus rhythm and of patients with chronic atrial fibrillation. Then, semiquantitative RT-PCR using 18S RNA as the "housekeeping gene" was performed. In patients with chronic atrial fibrillation, there were only mild reductions in mRNA expression of the alpha1c-subunit (-15.5 %, p = 0.13), and of the beta1-subunit isoforms a and c (-13.3 %, p = 0.14 and -16.6%, p = 0.18, respectively). However, mRNA expression of the alpha2/delta1-subunit (-31.5 %, p < 0.01) and of the beta1-subunit isoform b (-39.9 %, p < 0.0005) was significantly reduced in patients with chronic AF. Taken together, the mRNA expression of the beta1-subunit isoforms b and c, which are splice variants, was significantly down-regulated by 26.5 % (p < 0.05) in these patients. The analysis of the beta1c/beta1b ratio resulted in a significant shift by 39.2 % (p < 0.0001) in favor of beta1c in patients with chronic atrial fibrillation. In the AF patients, the abundance of the 5-HT4-receptor transcript was significantly reduced by 36 % (p < 0.05). The beta-adrenoreceptor transcription was unchanged. In both SR and AF patients, chronic beta-blocker treatment did neither significantly effect the mRNA expression of the L-type Ca2+-channel subunits, the beta-adrenoreceptor subtypes 1 and 2, nor that of the 5-HT4-receptor. Our data show that chronic AF is associated with a decrease in the atrial mRNA amount of auxiliary subunits of the L-type Ca2+-channel and of the 5-HT4-receptor. This supports the hypothesis that the observed alterations in mRNA transcription in AF patients may lead to a decrease in the availability of functional L-type Ca2+-channels and 5-HT4-receptors and/or reduce L-type Ca2+-current amplitude and density, thus, promoting and stabilizing the arrhythmia.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, L-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin
|
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0300-8428
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
96
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
82-90
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:11215536-Adrenergic beta-Antagonists,
pubmed-meshheading:11215536-Aged,
pubmed-meshheading:11215536-Atrial Fibrillation,
pubmed-meshheading:11215536-Calcium Channels, L-Type,
pubmed-meshheading:11215536-Female,
pubmed-meshheading:11215536-Gene Expression,
pubmed-meshheading:11215536-Humans,
pubmed-meshheading:11215536-Male,
pubmed-meshheading:11215536-Middle Aged,
pubmed-meshheading:11215536-Protein Isoforms,
pubmed-meshheading:11215536-RNA, Messenger,
pubmed-meshheading:11215536-Receptors, Adrenergic, beta,
pubmed-meshheading:11215536-Receptors, Serotonin
|
pubmed:year |
2001
|
pubmed:articleTitle |
Atrial L-type Ca2+-channel, beta-adrenorecptor, and 5-hydroxytryptamine type 4 receptor mRNAs in human atrial fibrillation.
|
pubmed:affiliation |
Deutsches Herzzentrum München, Klinik für Herz- und Gefässchirurgie.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|