Prolongation of action potential duration and QT interval during epilepsy linked to increased contribution of neuronal sodium channels to cardiac late Na+ current: potential mechanism for sudden death in epilepsy.
نویسندگان
چکیده
BACKGROUND Arrhythmias associated with QT prolongation on the ECG often lead to sudden unexpected death in epilepsy. The mechanism causing a prolongation of the QT interval during epilepsy remains unknown. Based on observations showing an upregulation of neuronal sodium channels in the brain during epilepsy, we tested the hypothesis that a similar phenomenon occurs in the heart and contributes to QT prolongation by altering cardiac sodium current properties (INa). METHODS AND RESULTS We used the patch clamp technique to assess the effects of epilepsy on the cardiac action potential and INa in rat ventricular myocytes. Consistent with QT prolongation, epileptic rats had longer ventricular action potential durations attributable to a sustained component of INa (INaL). The increase in INaL was because of a larger contribution of neuronal Na channels characterized by their high sensitivity to tetrodotoxin. As in the brain, epilepsy was associated with an enhanced expression of the neuronal isoform NaV1.1 in cardiomyocyte. Epilepsy was also associated with a lower INa activation threshold resulting in increased cell excitability. CONCLUSIONS This is the first study correlating increased expression of neuronal sodium channels within the heart to epilepsy-related cardiac arrhythmias. This represents a new paradigm in our understanding of cardiac complications related to epilepsy.
منابع مشابه
Prolongation of Action Potential Duration and QT Interval during Epilepsy Linked to Increased Contribution of Neuronal Sodium Channels to Cardiac Late Na Current: A Potential Mechanism for Sudden Death in Epilepsy
متن کامل
Increased Persistent Sodium Current Due to Decreased PI3K Signaling Contributes to QT Prolongation in the Diabetic Heart
Diabetes is an independent risk factor for sudden cardiac death and ventricular arrhythmia complications of acute coronary syndrome. Prolongation of the QT interval on the electrocardiogram is also a risk factor for arrhythmias and sudden death, and the increased prevalence of QT prolongation is an independent risk factor for cardiovascular death in diabetic patients. The pathophysiological mec...
متن کاملهای اسید گلوتامیک، تریپتوفان، آلانین tRNA بررسی مولکولی در Long QT وآسپارژین درژنوم میتوکندری بیماران مبتلا بهسندرم مقایسه با گروه کنترل
Background and purpose: Long QT syndrome is a heart arrhythmia identified by prolongation of the QT interval which is a cause of sudden cardiac death in young individuals. In most cases, abnormalities in heart repolarization are reasons of prolongation of action potential and arrhythmia. The activity of ion channels is sensitive to ATP level, therefore, mitochondrial disorders are considered...
متن کاملQT-Dispersion as a potential marker in prognosis of acute myocardial infarction
Introduction: QT dispersion in a 12 lead ECG represents the heterogeneity of ventricular repolarization. The prolongation of QT-interval dispersion increases the risk of coronary heart disease, ventricular arrhythmia, and sudden cardiac death in patients with myocardial infarction. We aimed to investigate the prognostic value of QT-dispersion in patients with acute myocardial infarction. Meth...
متن کاملAltered Cardiac Electrophysiology and SUDEP in a Model of Dravet Syndrome
OBJECTIVE Dravet syndrome is a severe form of intractable pediatric epilepsy with a high incidence of SUDEP: Sudden Unexpected Death in epilepsy. Cardiac arrhythmias are a proposed cause for some cases of SUDEP, yet the susceptibility and potential mechanism of arrhythmogenesis in Dravet syndrome remain unknown. The majority of Dravet syndrome patients have de novo mutations in SCN1A, resulting...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation. Arrhythmia and electrophysiology
دوره 8 4 شماره
صفحات -
تاریخ انتشار 2015