PMID- 30367153 OWN - NLM STAT- MEDLINE DCOM- 20191015 LR - 20200601 IS - 1745-7254 (Electronic) IS - 1671-4083 (Print) IS - 1671-4083 (Linking) VI - 40 IP - 6 DP - 2019 Jun TI - Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABA(A) receptors. PG - 755-761 LID - 10.1038/s41401-018-0168-6 [doi] AB - Propofol is an intravenous anesthetic that can active gamma-aminobutyric acid A (GABA(A)) receptors and generate sedative-hypnotic effects. Propofol has been widely applied clinically to achieve sedation comparable to sleep in humans. The basal forebrain (BF) is a brain region that plays an important role in sleep-wake regulation. Previous studies suggest that propofol affects the sleep-wake circuit via the BF; however, the mechanism remains elusive. In the current study we investigated the effects of propofol on the inherent properties of cholinergic neurons and their ability to convert excitatory inputs into spikes in mouse BF slices using whole-cell patch clamp recordings. Bath application of propofol (10 muM) significantly elevated the threshold potentials (Vts), decreased the number of spikes in response to a depolarizing current injection, and augmented the inter-spike intervals (ISIs), energy barrier (Vts-Vrs), and absolute refractory periods (ARPs). These effects were eliminated by co-application of a GABA(A) receptor antagonist picrotoxin (50 muM). Altogether, our results reveal that propofol decreases the excitability of cholinergic neurons in mouse BF via GABA(A) receptors. FAU - Chen, Lei AU - Chen L AD - Department of Pharmacology and Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. FAU - Yang, Zhi-Lai AU - Yang ZL AD - Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. FAU - Cheng, Juan AU - Cheng J AD - Department of Pharmacology and Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. FAU - Zhang, Ping-Ping AU - Zhang PP AD - Department of Pharmacology and Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. FAU - Zhang, Le-Sha AU - Zhang LS AD - Department of Pharmacology and Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. FAU - Liu, Xue-Sheng AU - Liu XS AD - Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. liu711029@hotmail.com. FAU - Wang, Lie-Cheng AU - Wang LC AD - Department of Pharmacology and Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. wangliecheng@ahmu.edu.cn. LA - eng PT - Journal Article DEP - 20181026 PL - United States TA - Acta Pharmacol Sin JT - Acta pharmacologica Sinica JID - 100956087 RN - 0 (Anesthetics, Intravenous) RN - 0 (Hypnotics and Sedatives) RN - 0 (Receptors, GABA-A) RN - YI7VU623SF (Propofol) SB - IM MH - Anesthetics, Intravenous/*pharmacology MH - Animals MH - Basal Forebrain/*drug effects MH - Cholinergic Neurons/*drug effects MH - Hypnotics and Sedatives/*pharmacology MH - Mice, Inbred C57BL MH - Propofol/*pharmacology MH - Receptors, GABA-A/*metabolism PMC - PMC6786414 OTO - NOTNLM OT - GABAA receptors OT - anesthesia OT - basal forebrain OT - cholinergic neurons OT - picrotoxin OT - propofol COIS- The authors declare no competing interests. EDAT- 2018/10/28 06:00 MHDA- 2019/10/16 06:00 PMCR- 2020/06/01 CRDT- 2018/10/28 06:00 PHST- 2018/03/13 00:00 [received] PHST- 2018/08/31 00:00 [accepted] PHST- 2018/10/28 06:00 [pubmed] PHST- 2019/10/16 06:00 [medline] PHST- 2018/10/28 06:00 [entrez] PHST- 2020/06/01 00:00 [pmc-release] AID - 10.1038/s41401-018-0168-6 [pii] AID - 168 [pii] AID - 10.1038/s41401-018-0168-6 [doi] PST - ppublish SO - Acta Pharmacol Sin. 2019 Jun;40(6):755-761. doi: 10.1038/s41401-018-0168-6. Epub 2018 Oct 26.