title: Propofol Regulates the Surface Expression of GABAA Receptors: Implications in Synaptic Inhibition.
abstract: BACKGROUND
  The anesthetic propofol is thought to induce rapid hypnotic sedation by potentiating γ-aminobutyric acid receptor (GABAAR) activity. Little is known about the molecular mechanisms of propofol in modulating inhibitory synaptic transmission. We aimed to investigate the role of propofol in modulating surface expression of GABAARs.
  
  
  METHODS
  C57BL/6 mice received an intraperitoneal injection of propofol. Hippocampal pyramidal neurons were prepared from embryonic day-18 mice and were treated with propofol. Proteins on the plasma membrane were analyzed using cell surface biotinylation, immunoblotting and enzyme-linked immunosorbent assay. Electrophysiological activities were recorded from hippocampal cells in acute brain slices of mice. The interaction between GABAARs and clathrin adaptor protein 2 was assessed by immunoprecipitation. Phosphorylation of GABAARs was shown by in vitro kinase assay.
  
  
  RESULTS
  Propofol facilitated membrane accumulation of GABAARβ3 subunits. Propofol mediated phosphorylation of GABAARβ3 by protein kinase Cε which blocked the interaction between GABAARβ3 and the β-adaptin subunit of adaptor protein 2, resulting in an inhibition of the receptor endocytosis in hippocampal pyramidal neurons. Coincident with increased GABAARs surface level, propofol enhanced evoked and miniature synaptic GABA receptor currents.
  
  
  CONCLUSIONS
  This study offers new insight on the regulatory mechanism of propofol in inhibiting neuronal excitability.
authors.affiliation: From the Departments of *Pharmacy and †Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.forename: Ruili
authors.initials: R
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Jia
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D015742:Propofol / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D006993:Hypnotics and Sedatives; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D015742:Propofol