Epilepsy Alters the Activity and Adrenergic Response of the Cardiac Sodium Current

Abstract

Abnormalities in cardiac rhythm or repolarization are observed in epilepsy. They appear during or shortly after seizure and include atrioventricular (AV) block, atrial fibrillation, supraventricular tachycardia, ventricular premature depolarization and bundle-branch block. The ECG recordings often show altered heart rate dynamics, indicative of changes in sympathovagal balance in epileptic patients. It has been suggested that autonomic imbalance induced remodelling of the heart and altered cardiac sympathetic response. To test this hypothesis we measured the response of the cardiac sodium current INa to isoproterenol in the rat epilepsy model (kainic acid). Using patch clamp technique on isolated ventricular myocytes we found that epilepsy by itself increased maximum INa density by 76% from 59±7 pA/pF to 104±20 pA/pF. Isoproterenol increased INa more importantly in epileptic rats than in control animals with respective changes of 93% and 127%. Mid-potential for steady-state activation was shifted from −42.9±0,3 mV in control to −55±1 mV in epileptic rats. Steady state mid-inactivation went from −79±1mV to −84±1 mV. Isoproterenol attenuated the differences in steady state parameters by bringing the activation and inactivation mid potential to −63±1 mV and −89±1mV respectively in sham and epileptic rats. We conclude that epilepsy modifies INa activity in a manner consistent with an increase in cardiac excitability. Moreover, the changes in gating parameters increase sodium entry into ventricular myocytes and may lead to calcium overload and associated delayed afterdepolarizations. These mechanisms may explain in part the arrhythmias observed in epileptic patients.