Propofol differentially induces unconsciousness and respiratory depression through distinct interactions between GABAA receptor and GABAergic neuron in corresponding nuclei.
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| Abstract |
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-Bötzinger 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.
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| Authors | Junli Jiang, Yingfu Jiao, Po Gao, Wen Yin, Wei Zhou, Yunchun Zhang, Yanjun Liu, Daxiang Wen, Yuan Wang, Liang Zhou, Tian Yu, Weifeng Yu |
| Journal | Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 53 Issue 8 Pg. 1076-1087 (Jul 28 2021) ISSN: 1745-7270 [Electronic] China |
| PMID | 34137445 (Publication Type: Journal Article) |
| Copyright | © The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: [email protected]. |
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