P264Sodium channel remodelling leads to cardiac conduction system dysmorphogenesis

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Abstract

Purpose

Several previous studies have revealed that increases of sodium currents (INa) seems to be an important factor in the prolongation of action potential duration and the generation of polymorphic ventricular tachycardia in repolarisation disorders, such as the long QT syndrome (Cardona K , 2010) which has been related to cases of sudden death in newborns (Roberts JD, and Gollob MH; 2010). Recently we have demonstrated that early sodium channel remodelling secondary to IKs blockage in a mouse model of long QT syndrome leads to morphological and functional anomalies of the ventricular conduction system during development which might further lead to cardiac hypertrophy (de la Rosa , in preparation).

Methods

To further assess the relationship between cardiac sodium currents remodelling and the conformation of the cardiac conduction system during development, we are currently designing and ex vivo system to increase INa current in Cx40-GFP embryos.

Results

We found that Cx40-GFP embryos treated with ATX-II toxin (which increases INa current,) display a significant decrease in the number of green ventricular trabeculations in the compared to control embryos indicating that increases in INa current in the developing heart leads to an abnormal ventricular conduction system configuration.

Conclusions

Here we provide the first direct evidence for a relationship between early sodium ion channels remodelling and the presence of morphological and/or functional anomalies of the ventricular conduction system in the developing heart. This study might shed new insights into understanding the mechanisms underlying cardiac electrophysiological disorders in newborns and may open new ways to better understand clinical pathologies such as cardiac congenital anomalies, arrhythmias and perinatal sudden death.

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