Postnatal development of transmural gradients in expression of ion channels and Ca²⁺-handling proteins in the ventricle

详细信息    查看全文

• 作者：Eman S.H. Abd Allah ; Oleg V. Aslanidi ; James O. Tellez ; Joseph Yanni ; Rudi Billeter ; Henggui Zhang ; Halina Dobrzynski ; Mark R. Boyett
• 关键词：Cardiac development ; Ion channels/membrane transport ; Gene expression ; Intracellular Ca2+ ; Arrhythmogenesis
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：53
• 期：2
• 页码：145-155
• 全文大小：2824 K

文摘

Transmural gradients in myocyte action potential duration (APD) and Ca²⁺-handling proteins are argued to be important for both the normal functioning of the ventricle and arrhythmogenesis. In rabbit, the transmural gradient in APD (left ventricular wedge preparation) is minimal in the neonate. During postnatal development, APD increases both in the epicardium and the endocardium, but the prolongation is more substantial in the endocardium leading to a significant transmural gradient. We have investigated changes in the expression of ion channels and also Ca²⁺-handling proteins in the subepicardial and subendocardial layers of the left ventricular free wall in neonatal (2-7 days of age) and adult male (~ 6 months of age) New Zealand White rabbits using quantitative PCR and also, when possible, in situ hybridisation and immunohistochemistry. In the adult, there were significant and substantial transmural gradients in Ca_v1.2, KChIP2, ERG, K_vLQT1, K_ir2.1, NCX1, SERCA2a and RyR2 at the mRNA and, in some cases, protein level¡ªin every case the mRNA or protein was more abundant in the epicardium than the endocardium. Of the eight transmural gradients seen in the adult, only three were observed in the neonate and, in two of these cases, the gradients were smaller than those in the adult. However, in the neonate there were also transmural gradients not observed in the adult: in HCN4, Na_v1.5, minK, K_ir3.1 and Cx40 mRNAs ¡ª in every case the mRNA was more abundant in the endocardium than the epicardium. If the postnatal changes in ion channel mRNAs are used to predict changes in ionic conductances, mathematical modelling predicts the changes in APD observed experimentally. It is concluded that many of the well known transmural gradients in the ventricle develop postnatally.