Intravenous anesthetics have differential effects on human potassium channels
General anesthetics are widely used in the clinic and greatly promote the development of surgery. However, the incidence of cardiovascular and respiratory complications caused by general anesthetics is still high, and the underlying mechanisms remain incompletely understood. Potassium channels are w...
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China Science Publishing & Media Ltd.
2024-09-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024151 |
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| author | Tao Ying Yao Kejie Wu Jing Xu Tian Lin Junhui Qin Yi Su Diansan Cai Shiqing Yu Weifeng Chen Xuemei |
| author_facet | Tao Ying Yao Kejie Wu Jing Xu Tian Lin Junhui Qin Yi Su Diansan Cai Shiqing Yu Weifeng Chen Xuemei |
| author_sort | Tao Ying |
| collection | DOAJ |
| description | General anesthetics are widely used in the clinic and greatly promote the development of surgery. However, the incidence of cardiovascular and respiratory complications caused by general anesthetics is still high, and the underlying mechanisms remain incompletely understood. Potassium channels are widely expressed in the heart and blood vessels and participate in regulating blood pressure, heart rate, and other physiological parameters. Whether they are directly affected by intravenous general anesthetics is unclear. Here, we independently express four classes of potassium channels, TASK-1, TASK-3, Kv1.5, Kv2.1, Kir2.1, SK1 and SK3, in Xenopus oocytes. The effects of propofol, pentobarbital and ketamine on these channels are evaluated by their current change. We find that propofol and ketamine potentiate TASK-3 and SK3 current respectively, while pentobarbital and ketamine inhibit SK1 current. To identify the key residues in TASK-3, SK1 and SK3 that interact with intravenous anesthetics, we predict homology models of the three channels and perform molecular docking simulations. The results show that propofol forms a hydrogen bond with Q126 of TASK-3, ketamine forms a hydrogen bond with S290 of SK1 and S467 of SK3, while pentobarbital forms hydrogen bonds with S330 and T358 of SK1. As these potassium channels are closely related to respiratory system regulation, cardiac rhythm and vasodilation, our study provides a new perspective for further study on the mechanism of general anesthetics-induced respiratory and circulatory side effects. |
| format | Article |
| id | doaj-art-d1ddb0a3133643b689a49ea5e32bc76a |
| institution | Kabale University |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | China Science Publishing & Media Ltd. |
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| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-d1ddb0a3133643b689a49ea5e32bc76a2025-08-20T03:53:47ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-09-01561594160310.3724/abbs.202415120d259ccIntravenous anesthetics have differential effects on human potassium channelsTao Ying0Yao Kejie1Wu Jing2Xu Tian3Lin Junhui4Qin Yi5Su Diansan6Cai Shiqing7Yu Weifeng8Chen Xuemei9["Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China"]["Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 101408, China"]["Department of Equipment and Materials, Biomedical R&D Project Team, Zhongshan Hospital, Fudan University, Shanghai 200031, China"]["Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China"]["Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China"]["Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China"]["Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China"]["Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 101408, China"]["Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China"]["Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China","Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai 200127, China"]General anesthetics are widely used in the clinic and greatly promote the development of surgery. However, the incidence of cardiovascular and respiratory complications caused by general anesthetics is still high, and the underlying mechanisms remain incompletely understood. Potassium channels are widely expressed in the heart and blood vessels and participate in regulating blood pressure, heart rate, and other physiological parameters. Whether they are directly affected by intravenous general anesthetics is unclear. Here, we independently express four classes of potassium channels, TASK-1, TASK-3, Kv1.5, Kv2.1, Kir2.1, SK1 and SK3, in Xenopus oocytes. The effects of propofol, pentobarbital and ketamine on these channels are evaluated by their current change. We find that propofol and ketamine potentiate TASK-3 and SK3 current respectively, while pentobarbital and ketamine inhibit SK1 current. To identify the key residues in TASK-3, SK1 and SK3 that interact with intravenous anesthetics, we predict homology models of the three channels and perform molecular docking simulations. The results show that propofol forms a hydrogen bond with Q126 of TASK-3, ketamine forms a hydrogen bond with S290 of SK1 and S467 of SK3, while pentobarbital forms hydrogen bonds with S330 and T358 of SK1. As these potassium channels are closely related to respiratory system regulation, cardiac rhythm and vasodilation, our study provides a new perspective for further study on the mechanism of general anesthetics-induced respiratory and circulatory side effects.https://www.sciengine.com/doi/10.3724/abbs.2024151general anestheticshypotensionrespiratory depressionpotassium channelsmolecular docking |
| spellingShingle | Tao Ying Yao Kejie Wu Jing Xu Tian Lin Junhui Qin Yi Su Diansan Cai Shiqing Yu Weifeng Chen Xuemei Intravenous anesthetics have differential effects on human potassium channels Acta Biochimica et Biophysica Sinica general anesthetics hypotension respiratory depression potassium channels molecular docking |
| title | Intravenous anesthetics have differential effects on human potassium channels |
| title_full | Intravenous anesthetics have differential effects on human potassium channels |
| title_fullStr | Intravenous anesthetics have differential effects on human potassium channels |
| title_full_unstemmed | Intravenous anesthetics have differential effects on human potassium channels |
| title_short | Intravenous anesthetics have differential effects on human potassium channels |
| title_sort | intravenous anesthetics have differential effects on human potassium channels |
| topic | general anesthetics hypotension respiratory depression potassium channels molecular docking |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024151 |
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