Propofol facilitates glutamatergic transmission to neurons of the ventrolateral preoptic nucleus

Ke Y. Li, Yan Zhong Guan, Kresimir Krnjević, Jiang H. Ye

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

BACKGROUND: There is much evidence that the sedative component of anesthesia is mediated by γ-aminobutyric acid type A (GABAA) receptors on hypothalamic neurons responsible for arousal, notably in the tuberomammillary nucleus. These GABAA receptors are targeted by γ-aminobutyric acid-mediated (GABAergic) neurons in the ventrolateral preoptic area (VLPO): When these neurons become active, they inhibit the arousal-producing nuclei and induce sleep. According to recent studies, propofol induces sedation by enhancing VLPO-induced synaptic inhibition, making the target cells more responsive to GABAA. The authors explored the possibility that propofol also promotes sedation less directly by facilitating excitatory inputs to the VLPO GABAergic neurons. METHODS: Spontaneous excitatory postsynaptic currents were recorded from VLPO cells-principally mechanically isolated, but also in slices from rats. RESULTS: In isolated VLPO GABAergic neurons, propofol increased the frequency of glutamatergic spontaneous excitatory postsynaptic currents without affecting their mean amplitude. The action of propofol was mimicked by muscimol and prevented by gabazine, respectively a specific agonist and antagonist at GABAA receptors. It was also suppressed by bumetanide, a blocker of Na-K-Cl cotransporter-mediated inward Cl transport. In slices, propofol also increased the frequency of spontaneous excitatory postsynaptic currents and, at low doses, accelerated firing of VLPO cells. CONCLUSION: Propofol induces sedation, at least in part, by increasing firing of GABAergic neurons in the VLPO, indirectly by activation of GABAA receptors on glutamatergic afferents: Because these axons/terminals have a relatively high internal Cl concentration, they are depolarized by GABAergic agents such as propofol, which thus enhance glutamate release.

Original languageEnglish (US)
Pages (from-to)1271-1278
Number of pages8
JournalAnesthesiology
Volume111
Issue number6
DOIs
StatePublished - Dec 2009

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

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