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

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 (I-Na).Methods and Results We used the patch clamp technique to assess the effects of epilepsy on the cardiac action potential and I-Na in rat ventricular myocytes. Consistent with QT prolongation, epileptic rats had longer ventricular action potential durations attributable to a sustained component of I-Na (I-NaL). The increase in I-NaL 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 Na(V)1.1 in cardiomyocyte. Epilepsy was also associated with a lower I-Na 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.