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 (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.
['Biet|Michael|M|', 'Morin|Nathalie|N|', 'Lessard-Beaudoin|Melissa|M|', 'Graham|Rona K|RK|', 'Duss|Sandra|S|', 'Gagné|Jonathan|J|', 'Sanon|Nathalie T|NT|', 'Carmant|Lionel|L|', 'Dumaine|Robert|R|']
D000200:Action Potentials D000818:Animals D001145:Arrhythmias, Cardiac D015153:Blotting, Western D004247:DNA D003645:Death, Sudden D004827:Epilepsy D005786:Gene Expression Regulation D008297:Male D032383:Myocytes, Cardiac D062554:NAV1.5 Voltage-Gated Sodium Channel D018408:Patch-Clamp Techniques D051381:Rats D060888:Real-Time Polymerase Chain Reaction
action potentials epilepsy sodium channels cardiac sudden death arrhythmias electrophysiology