| 研究課題/領域番号 |
22K20906
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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, 研究所, 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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| キーワード | KCND3 / potassium channel / early repolarization / epilepsy / Kv4.3 / patch-clamp method / sudden cardiac death |
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| 研究実績の概要 |
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.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
The study is progressing according to the plan. Results have been and planned to be disseminated in academic conferences (JCS2023 in March and Heart Rhythm Society Annual Meeting in May).
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| 今後の研究の推進方策 |
We have planned to apply several candidate drugs to the variant channels and some of the drugs would be applied.
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| 次年度使用額が生じた理由 |
This fiscal year, manual patch-clamp method has been performed to screen candidate drugs in wild and variant Ito channels, and next fiscal year we are planning to perform automated patch-clamp system (Patchliner by Nanion technologies) which would allow us to evaluate more candidate drugs in shorter time. Therefore, some preparations have been carried out including the development of a stable cell line and training to work in the new system.
Some findings were presented at the domestic conference, and in the next fiscal year, we will disseminate the results at the international conference.
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