Cortisol influences the ontogeny of both α- and β-subunits of the cardiac sodium channel in fetal sheep
Cortisol influences the ontogeny of both α- and β-subunits of the cardiac sodium channel in fetal sheep
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DOI：
10.1677/joe.0.1800449
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发表时间：
2004-03-01
影响因子：
4
通讯作者：
Vandenberg, JI
中科院分区：
文献类型：
--
作者：
Fahmi, AI;Forhead, AJ;Vandenberg, JI
在发育过程中，心脏必须适应形状、大小的变化，在出生时还必须适应动脉压的显著变化。心脏的有序收缩依赖于单个心肌细胞中适当密度的离子通道的协调表达。本研究表明，胎鼠心脏钠通道α亚基SCN5A在孕中期高表达，但在出生前10天开始下降，之后又开始升高。而β-亚基SCN1b在分娩时表达逐渐增加，而SCN3B在任何妊娠时间点都没有检测到表达。在正常的产前皮质醇激增之前，胎儿肾上腺切除导致SCN1b和SCN5A的7(.)0kb转录本的表达减少，但不是主要的8(.)5kb转录本。相反，向未成熟胎儿注射皮质醇可增加SCN1b和SCN5A 7(.)0kb转录本的表达水平。结果表明，皮质醇对妊娠晚期胎羊心脏SCN基因的表达有调节作用。这些发现可能对婴儿猝死综合征的病因学和成人心血管疾病的宫内规划有意义。
During development, the heart has to adapt to changes in shape, size and, at birth, to significant changes in arterial pressure. The orderly contraction of the heart is dependent on the coordinated expression of ion channels at appropriate densities in individual cardiac myocytes. The present study demonstrated that the expression of the alpha-subunit of the cardiac sodium channel, SCN5a, was high at mid gestation but then decreased until 10 days before birth before increasing again. Whereas the beta-subunit, SCN1b, gradually increased in expression towards partum, there was no detectable expression of SCN3b at any gestational time point. Fetal adrenalectomy prior to the normal prepartum surge in cortisol caused a reduction in expression of SCN1b and a 7(.)0 kb transcript of SCN5a, but not the major 8(.)5 kb transcript. Conversely, cortisol infusion into immature fetuses precociously increased expression levels of SCN1b and the SCN5a 7(.)0 kb transcript. The results show that cortisol regulates cardiac SCN gene expression in fetal sheep during late gestation. These findings could have implications for the aetiology of sudden infant death syndrome and for the intrauterine programming of adult cardiovascular disease.