厚朴酚通过与 G229 和 T225 位点结合抑制 TWIK1 通道。
The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites.
机构信息
Zhejiang Provincial Key Laboratory of Resources Protection and Innovation of Traditional Chinese Medicine, College of Food and Health, Zhejiang Agriculture and Forestry University, Hangzhou 311300, China.
Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China.
出版信息
Molecules. 2023 Sep 27;28(19):6815. doi: 10.3390/molecules28196815.
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 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 = 6.21 ± 0.13 μM). By molecular docking and alanine scanning mutagenesis, the IC 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.
TWIK1（K2P1.1/KCNK1）属于双孔域钾通道。其电流非常小，难以测量。在这项工作中，我们使用 100mM NH4+胞外液来增加在 HEK293 中稳定表达的细胞系中的 TWIK1 电流。然后，通过全细胞膜片钳实验观察厚朴酚对 TWIK1 的抑制作用，发现厚朴酚对 TWIK1 有显著的抑制作用（IC=6.21±0.13μM）。通过分子对接和丙氨酸扫描突变，TWIK1 突变体 G229A、T225A、I140A、L223A 和 S224A 的 IC 值分别为 20.77±3.20、21.81±7.93、10.22±1.07、9.55±1.62 和 7.43±3.20μM。因此，我们得出结论，厚朴酚对 TWIK1 通道的抑制作用与 P2-孔螺旋上的 G229 和 T225 有关。
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