2019 Fiscal Year Annual Research Report
Quantitative investigation of CaMKII-mediated TRPM4 regulation in atrial remodeling-associated arrhythmias
| Project/Area Number |
17K15566
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| Research Institution | Fukuoka University |
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Principal Investigator |
フ ヤオペン 福岡大学, 医学部, 助教 (40708476)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | protein interaction / TRPM4 / CaMKII |
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| Outline of Annual Research Achievements |
1)Co-localization of proteins was investigated by the confocal immunofluorescence and the Duolink proximity ligation assay (PLA) assay, which was helpful for the in situ detection of endogenous proteins in location with single molecule resolution. PLA signals denoted that TRPM4 and CaMKII protein were localized in close proximity. Incubation with AngII increased these PLA signals in HL-1 cells showing enhanced TRPM4-CaMKII interaction, which was consistent with that of confocal immunofluorescence microscopy.
2)Functional and physical implications of the TRPM4-CaMKII interaction had been confirmed by electrophysiological and fluorescent experiments. To test quantitative evaluation results on CaMKII-dependent TRPM4 modulation from previous cellular experiments, animal experiments were performed by langendorff apparatus with β-adrenergic activation which is known to stimulate CaMKII and enhance [Ca2+]i level in isolated perfused hearts. Strikingly, after isoproterenol perfusion, langendorff isolated hearts from TRPM4 knockout mice displayed more arrhythmias. This may be related to increased β-adrenergic response in TRPM4 knockout mice.
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