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 NH(4)(+) extracellular solution to increase TWIK1 current in its stable cell line expressed in HEK293. Then, the inhibition of magnolol on...

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Detalles Bibliográficos
Autores principales: Wang, Jintao, Liu, Huan, Sun, Zhuolin, Zou, Xinyi, Zhang, Zixuan, Wei, Xiaofeng, Pan, Lanying, Stalin, Antony, Zhao, Wei, Chen, Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574557/
https://www.ncbi.nlm.nih.gov/pubmed/37836658
http://dx.doi.org/10.3390/molecules28196815
Descripción
Sumario: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 NH(4)(+) 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 (IC(50) = 6.21 ± 0.13 μM). By molecular docking and alanine scanning mutagenesis, the IC(50) 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.

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