Propofol differentially induces unconsciousness and respiratory depression through distinct interactions between GABAa receptor and GABAergic neuron in corresponding nuclei  

作　　者：Junli Jiang Yingfu Jiao Po Gao Wen Yin Wei Zhou Yunchun Zhang Yanjun Liu Daxiang Wen Yuan Wang Liang Zhou Tian Yu Weifeng Yu 

机构地区：[1]Department of Anesthesiology,School of Medicine,Renji Hospital,Shanghai Jiao Tong University,Shanghai 200127,China [2]Guizhou Key Laboratory of Anesthesia and Organ Protection,Affiliated Hospital of Zunyi Medical University,Guizhou 563000,China [3]Guizhou Key Laboratory of Brain Science,Zunyi Medical University,Guizhou 563000,China [4]Department of Anesthesiology,Eye&ENT Hospital,Fudan University,Shanghai 200031,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第8期1076-1087,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.32030043 and 81970478);Shanghai Municipal Key Clinical Specialty(No.shslczdzk03601);Innovation Program of Shanghai Municipal Education Commission(No.2019-01-07-00-01-E00074);Shanghai Pudong New Area Municipal Commission of Health and Family Planning Funding(Nos.PW2015D-3 and PWZXQ2017-06 to W.F.).

摘　　要：Propofol is the most commonly used intravenous anesthetic worldwide.It can induce loss of consciousness prior to the occurrence of severe respiratory suppression,which is also a pharmacodynamic feature of all general anesthetics.However,the neural mechanisms underlying this natural phenomenon are controversial and highly related to patient safety.In the present study,we demonstrated that the pharmacodynamic effects of propofol(50 and 100 μM)on suppression of consciousness-related excitatory postsynaptic currents in the medial prefrontal cortex(mPFC)and centromedian nucleus of the thalamus(CMT)were lower than those in the kernel respiratory rhythmogenesis nucleus pre-Botzinger complex(PrBo).Furthermore,we unexpectedly found that the GABAa receptor β3 subunit is the key target for propofol's action and that it is mutually and exclusively expressed in GABAergic neurons.It is also more abundant in the mPFC and CMT,but mainly co-localized with GABAergic neurons in the PrBo.As a result,the differentiated expression pattern should mediate more neuron suppression through the activation of GABAergic neurons in the mPFC and CMT at low doses of propofol(50 μM).However,PrBo GABAergic neurons were only activated by propofol at a high dose(100 μM).These results highlight the detailed pharmacodynamic effects of propofol on consciousness-related and respiration-related nuclei and provide the distinct interaction mechanism between the β3 subunit and GABAergic neurons in mediating the suppression of consciousness compared to the inhibition of respiration.

关 键 词：PROPOFOL GABAa receptor GABAergic neuron respiratory depression 

分 类 号：R614[医药卫生—麻醉学]