| 研究課題/領域番号 |
20K16126
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| 研究機関 | 福岡大学 |
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研究代表者 |
胡 耀鵬 福岡大学, 医学部, 助教 (40708476)
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| 研究期間 (年度) |
2020-04-01 – 2023-03-31
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| キーワード | Arrhythmogenicity / TRPM4 / Nav1.5 |
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| 研究実績の概要 |
In the first year of our study, experiments were performed to characterize the interaction between Nav1.5 and TRPM4 channel. The results are summarized as follows: 1) TRPM4 and its mutant can form a multi-protein complex with Nav1.5. 2) Biotinylated membrane fraction revealed physical interaction between Nav1.5 and TRPM4 proteins at the cell surface, which suggested that the mutant may have more impact on the formation of the complex than the wild-type. 3）2D-simulation models incorporating TRPM4 channel and its mutant gating were constructed, which was helpful to interpret the mechanism of altered conduction.
During the first year, the results of our work on the implications of TRPM4 channel for cardiac arrhythmia were published in Pflugers Archiv-European Journal of Physiology and Cells.
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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
These experimental results address the functional implications of the Nav1.5-TRPM4 interaction. 2D-cardiomyocyte action potential model incorporating ion channel gating data enables in silico analysis of spatial electrophysiological parameters which would address why conduction abnormality occurs by the channelopathy.
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| 今後の研究の推進方策 |
To determine the functional impact of TRPM4 or its mutant on the gating kinetics of Nav1.5, the voltage-dependence of activation and inactivation will be determined by the patch clamp experiments. We will also check how endogenous Nav1.5 currents are affected in HL-1 cardiomyocytes when endogenous TRPM4 expression is upregulated under neuro-hormonal stresses.
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| 次年度使用額が生じた理由 |
In the next fiscal year, research costs will predominately focus on consumables for cell culture, molecular biological, biochemical and patch clamp experiments. To present the outcome of our study, we plan to submit experimental results to some academic journals.
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