Channelpedia

PubMed 22028338


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir2.1 , Kv1.4 , Kv3.1 , Kv4.2



Title: Activation of epidermal growth factor receptor mediates reperfusion arrhythmias in anaesthetized rats.

Authors: Mei Feng, Ji-Zhou Xiang, Zhang-Yin Ming, Qin Fu, Rong Ma, Qiu-Fang Zhang, Yao-Yan Dun, Lei Yang, Hui Liu

Journal, date & volume: Cardiovasc. Res., 2012 Jan 1 , 93, 60-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22028338


Abstract
Epidermal growth factor receptor (EGFR) plays a critical role in the development and function of the heart. Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart. The present study was designed to investigate whether EGFR activation would mediate cardiac arrhythmias induced by reperfusion in anaesthetized rats.Reperfusion arrhythmias were induced by 10 min ligation of the left anterior descending coronary artery, followed by a 30 min reperfusion in anaesthetized rats. The incidence and severity of cardiac arrhythmias were significantly reduced by pre-treatment with the EGFR kinase inhibitor AG556. The phosphorylation level of myocardial EGFR was increased during ischaemia and at early reperfusion. Intramyocardial transfection of EGFR siRNA reduced EGFR mRNA and protein, and decreased the incidence of ventricular fibrillation induced by reperfusion. Interestingly, tyrosine phosphorylation levels of cardiac Na(+) channels (I(Na)) and L-type Ca(2+) channels (I(Ca,L)) were significantly increased at time points corresponding to the alteration of EGFR phosphorylation levels during reperfusion. AG556 pre-treatment countered the increased tyrosine phosphorylation level of Na(+) and L-type Ca(2+) channels induced by reperfusion. Patch-clamp studies proved that AG556 could inhibit I(Na) and I(Ca,L) in rat ventricular myocytes. No significant alteration was observed in tyrosine phosphorylation levels of cardiac Kv4.2 and Kir2.1 channels during reperfusion.These results demonstrate for the first time that EGFR plays an important role in the genesis of arrhythmias induced by reperfusion, which is likely mediated at least in part by enhancing tyrosine phosphorylation of cardiac Na(+) and L-type Ca(2+) channels.