The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites-Reference-Cited by-同舟云学术

The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites

Published:2023-09-27 Issue:19 Volume:28 Page:6815
ISSN:1420-3049
Container-title:Molecules
language:en
Short-container-title:Molecules

Author:

Wang Jintao¹,Liu Huan¹,Sun Zhuolin¹,Zou Xinyi¹,Zhang Zixuan¹,Wei Xiaofeng¹,Pan Lanying²,Stalin Antony³^ORCID,Zhao Wei¹,Chen Yuan¹^ORCID

Affiliation:

1. 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

2. Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China

3. Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, China

Abstract

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.

Funder

Zhejiang Provincial Natural Science Foundation

Scientific Research & Development Fund of Zhejiang Shuren University

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

Link

https://www.mdpi.com/1420-3049/28/19/6815/pdf

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