Abstract 14308: Lamotrigine Inhibits the Inward Fast Sodium Current (I Na ) in Epileptic Rat Cardiomyocytes

Abstract

Introduction: Lamotrigine (LTG) is widely prescribed to treat neurological disorders such as migraine, neurophatic pain, and epilepsy. Recently, LTG has been linked to Brugada síndrome (BrS) ECG associated with a reduction in sodium current (I Na ) amplitude. Experimental studies have revealed that LTG blocks voltage gated sodium channels (VGSC). Hypothesis: Therefore, disrupting the depolarizing fast sodium inward current is a potential cause for arrhythmias. Recently our laboratory has shown that epilepsy induces molecular remodeling of the cardiac ventricle characterized by neuronal sodium channels overexpression, so it would be very plausible that LTG can cause important alterations on I Na in epileptic individuals. Methods: We used Patch-Clamp technique to test the effect of LTG on I Na in sham and epileptic rat ventricular cardiomyocytes. Results: We found that LTG inhibited I Na in a single dose-response manner with an IC 50 =326.35μM in sham rats. In epileptic rat cardiomyocytes the inhibitory effect was biphasic way with an IC 50 (1)=8.09 μM, which is close to the therapeutic range (between 12 and 50 μM), and a IC 50 (2)=333.66 μM. Moreover, LTG also altered sodium channels availability in biphasic manner with Vh(1)=-76.36 ± 0.31 mV and Vh(2)=-121.42 ± 1.38 mV, suggesting that LTG reduced the number of ion channels contributing to I Na . Conclusions: These findings may explain in part how LTG induce a Brugada pattern on the ECG of epileptic patients.