Referenced in: none

Automatically associated channels: Kv7.1 , Slo1

Title: Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis.

Authors: Angel J De La Rosa, Jorge N Domínguez, David Sedmera, Bara Sankova, Leif Hove-Madsen, Diego Franco, Amelia E Aránega

Journal, date & volume: Cardiovasc. Res., 2013 Jun 1 , 98, 504-14

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23542581

Abstract
Ion channel remodelling and ventricular conduction system (VCS) alterations play relevant roles in the generation of cardiac arrhythmias, but the interaction between ion channel remodelling and cardiac conduction system dysfunctions in an arrhythmogenic context remain unexplored.We have used a transgenic mouse line previously characterized as an animal model of Long QT Syndrome (LQTS) to analyse ion channel remodelling and VCS configuration. Reverse transcriptase-PCR and immunohistochemistry analysis showed early cardiac sodium channel upregulation at embryonic stages prior to the onset of Kv potassium channel remodelling, and cardiac hypertrophy at foetal stages. In line with these findings, patch-clamp assays demonstrated changes in sodium current density and a slowing of recovery from inactivation. Functional analysis by optical mapping revealed an immature ventricular activation pattern as well as an increase in the total left ventricle activation time in foetal transgenic hearts. Morphological analysis of LQTS transgenic mice in a Cx40(GFP/+)background demonstrated VCS dysmorphogenesis during heart development.Our data demonstrate early sodium channel remodelling secondary to IKs blockage in a mouse model of LQTS leading to morphological and functional anomalies in the developing VCS and cardiac hypertrophy. These results provide new insights into the mechanisms underlying foetal and neonatal cardiac electrophysiological disorders, which might help understand how molecular, functional, and morphological alterations are linked to clinical pathologies such as cardiac congenital anomalies, arrhythmias, and perinatal sudden death.