title: Propofol modulates phasic and tonic GABAergic currents in spinal ventral horn interneurones.
abstract: BACKGROUND
  Surgical interventions like skin incisions trigger withdrawal reflexes which require motor neurones and local circuit interneurones in the spinal ventral horn. This region plays a key role in mediating immobilizing properties of the GABAergic anaesthetic propofol. However, it is unclear how propofol modulates GABA(A) receptors in the spinal ventral horn and whether tonic or phasic inhibition is involved.
  
  
  METHODS
  Organotypic spinal cord tissue slices were prepared from mice. Whole-cell recordings were performed for quantifying effects of propofol on GABA(A) receptor-mediated phasic transmission and tonic conductance.
  
  
  RESULTS
  Propofol increased GABAergic phasic transmission by a prolongation of the decay time constant in a concentration-dependent manner. The amount of the charge transferred per inhibitory post-synaptic current, described by the area under the curve, was significantly augmented by 1 µM propofol (P<0.01). A GABA(A) receptor-mediated tonic current was not induced by 1 µM propofol but at a concentration of 5 µM (P<0.05).
  
  
  CONCLUSIONS
  Propofol depresses ventral horn interneurones predominantly by phasic rather than by tonic GABA(A) receptor-mediated inhibition. However, the present results suggest that the involvement of a tonic inhibition might contribute to the efficacy of propofol to depress nociceptive reflexes at high concentrations of the anaesthetic.
authors.affiliation: Experimental Anaesthesiology Section, Department of Anaesthesiology and Intensive Care, Eberhard-Karls-University, Tübingen, Germany veit-simon.eckle@uni-tuebingen.de.
authors.forename: V S
authors.initials: VS
authors.lastname: Eckle
authors.affiliation: Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, MA, USA.
authors.forename: U
authors.initials: U
authors.lastname: Rudolph
authors.affiliation: Experimental Anaesthesiology Section, Department of Anaesthesiology and Intensive Care, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Antkowiak
authors.affiliation: Experimental Anaesthesiology Section, Department of Anaesthesiology and Intensive Care, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Grasshoff
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects*; D007395:Interneurons / Q000187:drug effects*; D051379:Mice; D018408:Patch-Clamp Techniques / Q000379:methods; D015742:Propofol / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D015742:Propofol
keywords: anaesthetics i.v., propofol; brain, anaesthesia, molecular effects; ions, ion channels, pharmacology; pharmacology, propofol; spinal cord, GABA