Quantitative mRNA analysis of serotonin 5-HT4 receptor isoforms, calcium handling proteins and ion channels in human atrial fibrillation
Quantitative mRNA analysis of serotonin 5-HT4 receptor isoforms, calcium handling proteins and ion channels in human atrial fibrillation
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DOI：
10.1016/j.bbrc.2007.03.124
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发表时间：
2007-05-25
影响因子：
3.1
通讯作者：
Bril, Antoine
中科院分区：
文献类型：
--
作者：
Lezoualc'h, Frank;Steplewski, Klaudia;Bril, Antoine
5-羟色胺5-HT4受体存在于人的心房肌细胞中，并被认为与心房颤动(AF)的发生有关。在这里，我们对慢性房颤(CAF)和急性房颤(AAF)患者右心耳5-HT4受体和其他参与心律和收缩的关键基因进行了定量研究。11例窦性心律(SR)患者，5例房颤(AAF)患者，6例CAF患者(12个月)获得右心耳。对总RNA进行TaqMan实时定量RT-PCR。结果被归一化为三种看家基因的平均值，即亲环素、GADPH和RL-19。在SR患者组中，h5-HT4受体变异体的表达顺序为(B)>；(A)>；(G)>；(C)。在AAF中，我们发现h5-hT4(B)、h5-hT4(C)和h5-hT4(G)转录本显著减少。在CAF患者中，h5-HT4(B)亚型的mRNA表达水平显著高于SR两倍。β(1)-肾上腺素能受体、连接蛋白43和L型钙通道CaC-NA1C亚单位也有类似的增加。有趣的是，CAF与Na+/Ca~(2+)交换蛋白和电压依赖性Na~+通道SCN5A亚基的表达显著增加有关。我们的结果表明，h5-HT4(B)是人5-HT4受体的点状心脏亚型，在CAF中其表达增加。这些数据支持5-HT4受体参与房性心律失常。(C)2007 Elsevier Inc.保留所有权利。
Serotonin 5-HT4 receptors are present in human atrial myocytes and have been proposed to contribute to the generation of atrial fibrillation (AF). Here, we quantified 5-HT4 receptors as well as other key genes involved in cardiac rhythm and contraction in right atrial appendages of patients with chronic AF (CAF) and acute AF (AAF). Right atrial appendages were obtained from eleven patients in sinus rhythm (SR), five with AAF and six with CAF (>12 months). TaqMan real time quantitative RT-PCR was performed on total RNA. Results were normalised to the average of three housekeeping genes, cyclophilin, GADPH and RL-19. The rank order of expression of h5-HT4 receptors variants was (b) > (a) > (g) > (c) in the group of patients in SR. In AAF, we found a strong decrease in h5-HT4(b), h5-HT4(c), and h5-HT4(g) transcripts. In CAF patients, the mRNA expression level of the h5-HT4(b) isoform significantly increased two fold versus SR. A similar increase was reported for beta(1)-adrenergic receptor, connexin 43 and the L-type Ca2+ channel CaC-NA1C subunit. Interestingly, CAF was associated with a strong increase in the expression of Na+/Ca2+ exchanger and the voltage-dependent Na+ channel SCN5A subunit. Our results indicate that h5-HT4(b) is the dot minant cardiac isoform of human 5-HT4 receptors and its expression is increased in CAF. These data support the involvemen of 5-HT4 receptors in atrial arrhythmia. (c) 2007 Elsevier Inc. All rights reserved.