2023 Fiscal Year Annual Research Report
Functional and pharmacological investigation on novel KCND3 variants identified in patients with early repolarization syndrome and refractory epilepsy
| Project/Area Number |
22K20906
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
ビャムバジャブ ツェレンハム 国立研究開発法人国立循環器病研究センター, オープンイノベーションセンター, リサーチフェロー (60963527)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Keywords | potassium channel / Kv4.3 variants / electrophysiology / gain-of-function / neurological disorders |
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| Outline of Annual Research Achievements |
Sudden Unexpected Death in Epilepsy (SUDEP) is one of the most frequent causes of death in patients with refractory epilepsy (RE). We identified two novel KCND3 variants in young patients with RE though the functional properties of these variants have not been elucidated. We aimed to elucidate the electrophysiological changes of novel KCND3 variants and to analyze the pharmacological effect to the variants. 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, slow inactivation and slow recovery from inactivation. We investigated promising effects of candidate medicines.
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