2020 Fiscal Year Research-status Report
Investigation on the arrhythmogenecity of Nav1.5-TRPM4 channel complex
| Project/Area Number |
20K16126
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| Research Institution | Fukuoka University |
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Principal Investigator |
胡 耀鵬 福岡大学, 医学部, 助教 (40708476)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Arrhythmogenicity / TRPM4 / Nav1.5 |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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| Causes of Carryover |
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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