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...

Descripción completa

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
_version_ 1785120720538304512
author Wang, Jintao
Liu, Huan
Sun, Zhuolin
Zou, Xinyi
Zhang, Zixuan
Wei, Xiaofeng
Pan, Lanying
Stalin, Antony
Zhao, Wei
Chen, Yuan
author_facet Wang, Jintao
Liu, Huan
Sun, Zhuolin
Zou, Xinyi
Zhang, Zixuan
Wei, Xiaofeng
Pan, Lanying
Stalin, Antony
Zhao, Wei
Chen, Yuan
author_sort Wang, Jintao
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10574557
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105745572023-10-14 The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites Wang, Jintao Liu, Huan Sun, Zhuolin Zou, Xinyi Zhang, Zixuan Wei, Xiaofeng Pan, Lanying Stalin, Antony Zhao, Wei Chen, Yuan Molecules Communication 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. MDPI 2023-09-27 /pmc/articles/PMC10574557/ /pubmed/37836658 http://dx.doi.org/10.3390/molecules28196815 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Wang, Jintao
Liu, Huan
Sun, Zhuolin
Zou, Xinyi
Zhang, Zixuan
Wei, Xiaofeng
Pan, Lanying
Stalin, Antony
Zhao, Wei
Chen, Yuan
The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites
title The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites
title_full The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites
title_fullStr The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites
title_full_unstemmed The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites
title_short The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites
title_sort inhibitory effect of magnolol on the human twik1 channel is related to g229 and t225 sites
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574557/
https://www.ncbi.nlm.nih.gov/pubmed/37836658
http://dx.doi.org/10.3390/molecules28196815
work_keys_str_mv AT wangjintao theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT liuhuan theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT sunzhuolin theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT zouxinyi theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT zhangzixuan theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT weixiaofeng theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT panlanying theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT stalinantony theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT zhaowei theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT chenyuan theinhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT wangjintao inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT liuhuan inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT sunzhuolin inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT zouxinyi inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT zhangzixuan inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT weixiaofeng inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT panlanying inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT stalinantony inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT zhaowei inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites
AT chenyuan inhibitoryeffectofmagnololonthehumantwik1channelisrelatedtog229andt225sites

Ejemplares similares