Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

Stuart J. McDougall, Timothy W. Bailey, David Mendelowitz, Michael Andresen

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The anesthetic propofol is thought to induce rapid hypnotic sedation by facilitating a GABAergic tonic current in forebrain neurons. The depression of cardiovascular and respiratory regulation often observed during propofol suggests potential additional actions within the brainstem. Here we determined the impacts of propofol on both GABAergic and glutamatergic synaptic mechanisms in a class of solitary tract nucleus (NTS) neurons common to brainstem reflex pathways. In horizontal brainstem slices, we recorded from NTS neurons directly activated by solitary tract (ST) axons. We identified these second-order NTS neurons by time-invariant ("jitter" <200 μs), "all-or-none" glutamatergic excitatory postsynaptic currents (EPSCs) in response to shocks to the ST. In order to assess propofol actions, we measured ST-evoked, spontaneous and miniature EPSCs and inhibitory postsynaptic currents (IPSCs) during propofol exposure. Propofol prolonged miniature IPSC decay time constants by 50% above control at 1.8 μM. Low concentrations of gabazine (SR-95531) blocked phasic GABA currents. At higher concentrations, propofol (30 μM) induced a gabazine-insensitive tonic current that was blocked by picrotoxin or bicuculline. In contrast, total propofol concentrations up to 30 μM had no effect on EPSCs. Thus, propofol enhanced phasic GABA events in NTS at lower concentrations than tonic current induction, opposite to the relative sensitivity observed in forebrain regions. These data suggest that therapeutic levels of propofol facilitate phasic (synaptic) inhibitory transmission in second-order NTS neurons which likely inhibits autonomic reflex pathways during anesthesia.

Original languageEnglish (US)
Pages (from-to)552-563
Number of pages12
JournalNeuropharmacology
Volume54
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Solitary Nucleus
Propofol
Neurons
Excitatory Postsynaptic Potentials
Brain Stem
Inhibitory Postsynaptic Potentials
Prosencephalon
gamma-Aminobutyric Acid
Reflex
Autonomic Pathways
Picrotoxin
Bicuculline
Hypnotics and Sedatives
Synaptic Transmission
Respiratory Insufficiency
Action Potentials
Axons
Anesthetics
Shock
Anesthesia

Keywords

  • Anesthetic
  • Brainstem
  • Excitatory postsynaptic current
  • Glutamate
  • Inhibitory postsynaptic current
  • Propofol

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS). / McDougall, Stuart J.; Bailey, Timothy W.; Mendelowitz, David; Andresen, Michael.

In: Neuropharmacology, Vol. 54, No. 3, 03.2008, p. 552-563.

Research output: Contribution to journalArticle

McDougall, Stuart J. ; Bailey, Timothy W. ; Mendelowitz, David ; Andresen, Michael. / Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS). In: Neuropharmacology. 2008 ; Vol. 54, No. 3. pp. 552-563.
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