Abstracts

Rationale: Cardiac electrophysiological dysfunction is common in people with epilepsy; particularly in those with a longer duration of epilepsy. As a result people with epilepsy can suffer from serious cardiac arrhythmias, often precipitated by a seizure, which could contribute to their substantially increased risk of Sudden Unexpected Death in EPilepsy (SUDEP). Recent research from our laboratory has found in chronic rat models of genetic (Genetic Absence Rats from Strasbourg, GAERS) and acquired epilepsy (post-status epilepticus rats, post-SE) that heart function was detrimentally altered and there was decreased expression in the heart of a group of ion channels important in regulating cardiac cellular excitability and rhythm, Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels1. Here we investigated whether there was also altered expression of another group of ion channel that importantly contributes to cardiac automaticity and excitability, T-type calcium channels2,3.Methods: Chronically epileptic post-SE rats, GAERS, and non-epileptic control rats (NEC), had in vivo EEG and ECG recordings acquired continuously for 1 week which were analysed in a blinded manner. The hearts were collected, dissected into 4 chambers and snap frozen. T-type calcium channel (Cav3.1 and Cav3.2) and HCN channel (HCN2 and HCN4) mRNA expression was measured using qPCR.Results: The in-vivo cardiac ECG recordings demonstrated a consistent and striking bradycardia was associated with the onset of ictal activity in post-SE rats. There was also a significant increase in the in vivo sdRR interval (a measure a beat-to-beat variability) in post-SE rats during ictal activity (n=3) compared to interictal activity (n=8, p<0.05). Cav3.1 and Cav3.2 mRNA expression was significantly increased in the left (Cav3.1 p=0.08 and Cav3.2 p<0.05) and right ventricles (p<0.05 for Cav3.1 & Cav3.2) of post-SE rats (n=8) compared to controls (n=11). Similarly, Cav3.2 mRNA expression was significantly increased in the left (Cav3.2 p<0.001) and right ventricles (Cav3.2 p<0.001) of GAERS (n=8) compared to NEC (n=8). There was no significant change in T-type calcium channel mRNA expression in the left and right atria of both genetic and acquired models. Increases in HCN2 and HCN4 mRNA expression in the cardiac chambers of the epileptic rats was found, consistent with the findings of our previous study1.Conclusions: Altered expression of ion channels, T-type calcium and HCN channels are found in chronically epileptic rats, with both a genetic and acquired aetiology. The direction of change in expression is opposite, with the former being increased and the latter decreased. These results demonstrate that chronic epilepsy can result in complex cardiac channelopathies, which may have relevance for the pathophysiology of cardiac dysfunction in patients with epilepsy. 1. Powell KL, et al. Epilepsia 2014 55(4):609-20. 2. Mangoni ME, et al. Circ Res. 2006 98(11):1422-30. 3. Chiang CS, et al. Circ Res. 2009 104(4):522-30.