Intravenous anesthetics have differential effects on human potassium channels  

作　　者：Ying Tao Kejie Yao Jing Wu Tian Xu Junhui Lin Yi Qin Diansan Su Shiqing Cai Weifeng Yu Xuemei Chen 

机构地区：[1]Department of Anesthesiology,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China [2]Key Laboratory of Anesthesiology(Shanghai Jiao Tong University),Ministry of Education,Shanghai 200127,China [3]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 [4]University of Chinese Academy of Sciences,Beijing 101408,China [5]Department of Equipment and Materials,Biomedical R&D Project Team,Zhongshan Hospital,Fudan University,Shanghai 200031,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第11期1594-1603,共10页生物化学与生物物理学报(英文版)

基　　金：This work was supported by the grants from the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2023-JKCS-16 to X.C.);the National Natural Science Foundation of China(Nos.81874371 to X.C.,and 82201369 to Y.Q.);Shanghai Engineering Research Center of Perioperative Organ Support and Function Preservation(No.20DZ2254200 to W.Y.);Shanghai Municipal Key Clinical Specialty(No.shslczdzk03601 to W.Y.)。

摘　　要：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.

关 键 词：general anesthetics HYPOTENSION respiratory depression potassium channels molecular docking 

分 类 号：Q26[生物学—细胞生物学]