Harrell M D, Harbi S, Hoffman J F, Zavadil J, Coetzee W A
Pediatric Cardiology, New York University School of Medicine, New York, New York 10016, USA.
Physiol Genomics. 2007 Feb 12;28(3):273-83. doi: 10.1152/physiolgenomics.00163.2006. Epub 2006 Sep 19.
The immature and mature heart differ from each other in terms of excitability, action potential properties, contractility, and relaxation. This includes upregulation of repolarizing K(+) currents, an enhanced inward rectifier K(+) (Kir) current, and changes in Ca(2+), Na(+), and Cl(-) currents. At the molecular level, the developmental regulation of ion channels is scantily described. Using a large-scale real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay, we performed a comprehensive analysis of ion channel transcript expression during perinatal development in the embryonic (embryonic day 17.5), neonatal (postnatal days 1-2), and adult Swiss-Webster mouse hearts. These data are compared with publicly available microarray data sets (Cardiogenomics project). Developmental mRNA expression for several transcripts was consistent with the published literature. For example, transcripts such as Kir2.1, Kir3.1, Nav1.5, Cav1.2, etc. were upregulated after birth, whereas others [e.g., Ca(2+)-activated K(+) (KCa)2.3 and minK] were downregulated. Cl(-) channel transcripts were expressed at higher levels in immature heart, particularly those that are activated by intracellular Ca(2+). Defining alterations in the ion channel transcriptome during perinatal development will lead to a much improved understanding of the electrophysiological alterations occurring in the heart after birth. Our study may have important repercussions in understanding the mechanisms and consequences of electrophysiological alterations in infants and may pave the way for better understanding of clinically relevant events such as congenital abnormalities, cardiomyopathies, heart failure, arrhythmias, cardiac drug therapy, and the sudden infant death syndrome.
未成熟心脏和成熟心脏在兴奋性、动作电位特性、收缩性及舒张方面存在差异。这包括复极化钾离子电流上调、内向整流钾离子(Kir)电流增强以及钙离子、钠离子和氯离子电流的变化。在分子水平上,离子通道的发育调控鲜有描述。我们采用大规模实时定量逆转录聚合酶链反应(qRT-PCR)分析方法,对胚胎期(胚胎第17.5天)、新生期(出生后第1 - 2天)及成年瑞士韦伯斯特小鼠心脏围产期发育过程中的离子通道转录本表达进行了全面分析。这些数据与公开可用的微阵列数据集(心脏基因组学项目)进行了比较。几种转录本的发育性mRNA表达与已发表文献一致。例如,Kir2.1、Kir3.1、Nav1.5、Cav1.2等转录本在出生后上调,而其他一些转录本[如钙激活钾离子(KCa)2.3和minK]则下调。氯离子通道转录本在未成熟心脏中表达水平较高,尤其是那些由细胞内钙离子激活的转录本。明确围产期发育过程中离子通道转录组的变化,将有助于更深入地理解出生后心脏发生的心电生理变化。我们的研究可能对理解婴儿心电生理变化的机制和后果具有重要影响,并可能为更好地理解先天性异常、心肌病、心力衰竭、心律失常、心脏药物治疗及婴儿猝死综合征等临床相关事件铺平道路。