The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites
TWIK1 (K2P1.1/KCNK1) belongs to the potassium channels of the two-pore domain. Its current is very small and difficult to measure. In this work, we used a 100 mM NH4+ extracellular solution to increase TWIK1 current in its stable cell line expressed in HEK293. Then, the inhibition of magnolol on TWIK1 was observed via a whole-cell patch clamp experiment, and it was found that magnolol had a significant inhibitory effect on TWIK1 (IC50 = 6.21 ± 0.13 μM). By molecular docking and alanine scanning mutagenesis, the IC50 of TWIK1 mutants G229A, T225A, I140A, L223A, and S224A was 20.77 ± 3.20, 21.81 ± 7.93, 10.22 ± 1.07, 9.55 ± 1.62, and 7.43 ± 3.20 μM, respectively. Thus, we conclude that the inhibition of the TWIK1 channel by magnolol is related to G229 and T225 on the P2- pore helix.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Molecules (Basel, Switzerland) - 28(2023), 19 vom: 27. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jintao [VerfasserIn] |
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| Links: |
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| Themen: |
001E35HGVF |
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| Anmerkungen: |
Date Completed 01.11.2023 Date Revised 01.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/molecules28196815 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363296182 |
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| 500 | |a Date Revised 01.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a TWIK1 (K2P1.1/KCNK1) belongs to the potassium channels of the two-pore domain. Its current is very small and difficult to measure. In this work, we used a 100 mM NH4+ extracellular solution to increase TWIK1 current in its stable cell line expressed in HEK293. Then, the inhibition of magnolol on TWIK1 was observed via a whole-cell patch clamp experiment, and it was found that magnolol had a significant inhibitory effect on TWIK1 (IC50 = 6.21 ± 0.13 μM). By molecular docking and alanine scanning mutagenesis, the IC50 of TWIK1 mutants G229A, T225A, I140A, L223A, and S224A was 20.77 ± 3.20, 21.81 ± 7.93, 10.22 ± 1.07, 9.55 ± 1.62, and 7.43 ± 3.20 μM, respectively. Thus, we conclude that the inhibition of the TWIK1 channel by magnolol is related to G229 and T225 on the P2- pore helix | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a TWIK1 | |
| 650 | 4 | |a magnolol | |
| 650 | 4 | |a two-pore domain potassium channel | |
| 650 | 7 | |a magnolol |2 NLM | |
| 650 | 7 | |a 001E35HGVF |2 NLM | |
| 650 | 7 | |a Potassium Channels |2 NLM | |
| 650 | 7 | |a Biphenyl Compounds |2 NLM | |
| 700 | 1 | |a Liu, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Zhuolin |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Xinyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xiaofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Lanying |e verfasserin |4 aut | |
| 700 | 1 | |a Stalin, Antony |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuan |e verfasserin |4 aut | |
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