Propofol modulates phasic and tonic GABAergic currents in spinal ventral horn interneurones

V. S. Eckle, U. Rudolph, B. Antkowiak, C. Grasshoff

Research output: Contribution to journalArticlepeer-review

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) receptormediated 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 mM (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.

Original languageEnglish (US)
Pages (from-to)491-498
Number of pages8
JournalBritish Journal of Anaesthesia
Volume114
Issue number3
DOIs
StatePublished - Mar 2015
Externally publishedYes

Keywords

  • Anaesthetics i.v. propofol
  • Brain anaesthesia molecular effects
  • Ions ion channels pharmacology
  • Pharmacology propofol
  • Spinal cord GABA

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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