Propofol facilitates glutamatergic transmission to neurons of the ventrolateral preoptic nucleus.
Anesthesiology
; 111(6): 1271-8, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19934872
ABSTRACT
BACKGROUND:
There is much evidence that the sedative component of anesthesia is mediated by gamma-aminobutyric acid type A (GABA(A)) receptors on hypothalamic neurons responsible for arousal, notably in the tuberomammillary nucleus. These GABA(A) receptors are targeted by gamma-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 GABA(A). 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 GABA(A) 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 GABA(A) 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.
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Base de dados:
MEDLINE
Assunto principal:
Área Pré-Óptica
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Propofol
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Transmissão Sináptica
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Anestésicos Intravenosos
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Glutamatos
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article