Functional and pharmacological investigation on novel KCND3 variants identified in patients with early repolarization syndrome and refractory epilepsy

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The aim of this study is to elucidate the electrophysiological changes of novel KCND3 variants and to analyze the pharmacological effect of drugs to the variants. The variants are the cause of refractory epilepsy and might be related with early repolarization syndrome leading to sudden cardiac death in epilepsy (SUDEP).We have successfully created a cultured cell model with transiently expressing KCND3 encoding Kv4.3. The variant Ito channels caused gain-of-function effect: increase of Ito densities, leftward movement of activation and inactivation curves and slow inactivation. In addition, the variant showed slow recovery from inactivation. Therefore, we have applied some candidate drugs to variant channels and identified their promising effects.