RGD Reference Report - Activation of epidermal growth factor receptor mediates reperfusion arrhythmias in anaesthetized rats. - Rat Genome Database

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

Authors: Feng, Mei  Xiang, Ji-Zhou  Ming, Zhang-Yin  Fu, Qin  Ma, Rong  Zhang, Qiu-Fang  Dun, Yao-Yan  Yang, Lei  Liu, Hui 
Citation: Feng M, etal., Cardiovasc Res. 2012 Jan 1;93(1):60-8. doi: 10.1093/cvr/cvr281. Epub 2011 Oct 25.
RGD ID: 38676260
Pubmed: PMID:22028338   (View Abstract at PubMed)
DOI: DOI:10.1093/cvr/cvr281   (Journal Full-text)


AIMS: 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.
METHODS AND RESULTS: 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.
CONCLUSION: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Ventricular Fibrillation treatmentISOEgfr (Rattus norvegicus)38676260; 38676260 RGD 
Ventricular Fibrillation treatmentIMP 38676260 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)

Genes (Mus musculus)
Egfr  (epidermal growth factor receptor)

Genes (Homo sapiens)
EGFR  (epidermal growth factor receptor)


Additional Information