| 研究課題/領域番号 |
22K20906
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| 研究種目 |
研究活動スタート支援
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| 配分区分 | 基金 |
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| 審査区分 |
0902:内科学一般およびその関連分野
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| 研究機関 | 国立研究開発法人国立循環器病研究センター |
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研究代表者 |
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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| 研究期間 (年度) |
2022-08-31 – 2024-03-31
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| 研究課題ステータス |
完了 (2023年度)
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| 配分額 *注記 |
2,860千円 (直接経費: 2,200千円、間接経費: 660千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | potassium channel / Kv4.3 variants / electrophysiology / gain-of-function / neurological disorders / KCND3 / early repolarization / epilepsy / Kv4.3 / patch-clamp method / sudden cardiac death / arrhythmia / SSRIs / refractory epilepsy |
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| 研究開始時の研究の概要 |
KCND3 variants were identified in patients, and the pathogenicity of these variants have not been elucidated. We have already constructed the plasmid with these KCND3 variants. Using cultured cells transfected with KCND3 variants, I try to elucidate the electrophysiological mechanism of early repolarization (RE) by patch-clamp method, and the analysis will be beneficial for the elucidation of the pathogenesis of SUDEP. Next, I search for effective therapeutic agents for pediatric patients with RE.
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| 研究実績の概要 |
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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