a proton leak current through the cardiac sodium channel is linked to mixed arrhythmia and the dilated cardiomyopathy phenotype一个质子漏电流通过心脏钠离子通道与混合心律失常和扩张型心肌病的表型.pdfVIP

A Proton Leak Current through the Cardiac Sodium Channel Is Linked to Mixed Arrhythmia and the Dilated Cardiomyopathy Phenotype 1 2,3,4 1 ´ 1 ´ 1¤ Pascal Gosselin-Badaroudine , Dagmar I. Keller , Hai Huang , Valerie Pouliot , Aurelien Chatelier , 3 4 1,5 Stefan Osswald , Marijke Brink , Mohamed Chahine * 1 Laval University Robert-Giffard Research Centre, Quebec City, Quebec, Canada, 2 Cardiology Department, University Hospital Zurich, Zurich, Switzerland, 3 Cardiology Department, University Hospital Basel, Basel, Switzerland, 4 Cardiobiology Research Laboratories, University Hospital Basel, Basel, Switzerland, 5 Department of Medicine, Laval University, Quebec City, Quebec, Canada Abstract Cardiac Na+ channels encoded by the SCN5A gene are essential for initiating heart beats and maintaining a regular heart rhythm. Mutations in these channels have recently been associated with atrial fibrillation, ventricular arrhythmias, conduction disorders, and dilated cardiomyopathy (DCM). We investigated a young male patient with a mixed phenotype composed of documented conduction disorder, atrial flutter, and ventricular tachycardia associated with DCM. Further family screening revealed DCM in the patient’s mother and sister and in three of the mother’s sisters. Because of the complex clinical phenotypes, we screened SCN5A and identified a novel mutation, R219H, which is located on a highly conserved region on the fourth helix of the voltage sensor domain of Nav 1.5. Three family members with DCM carri