Source:http://linkedlifedata.com/resource/pubmed/id/18094320
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-2-25
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pubmed:abstractText |
Volatile anesthetics are used clinically to produce analgesia, amnesia, unconsciousness, blunted autonomic responsiveness, and immobility. Previous work has shown that the volatile anesthetic isoflurane, at concentrations that produce unconsciousness (250-500 microM), enhances fast synaptic inhibition in the brain mediated by GABA(A) receptors (GABA(A)-Rs). In addition, isoflurane causes sedation at concentrations lower than those required to produce unconsciousness or analgesia. In this study, we found that isoflurane, at low concentrations (25-85 microM) associated with its sedative actions, elicits a sustained current associated with a conductance increase in thalamocortical neurons in the mouse ventrobasal (VB) nucleus. These isoflurane-evoked currents reversed polarity close to the Cl(-) equilibrium potential and were totally blocked by the GABA(A)-R antagonist gabazine. Isoflurane (25-250 microM) produced no sustained current in VB neurons from GABA(A)-R alpha(4)-subunit knockout (Gabra4(-/-)) mice, although 250 microM isoflurane enhanced synaptic inhibition in VB neurons from both wild-type and Gabra4(-/-) mice. These data indicate an obligatory requirement for alpha(4)-subunit expression in the generation of the isoflurane-activated current. In addition, isoflurane directly activated alpha(4)beta(2)delta GABA(A)-Rs expressed in human embryonic kidney 293 cells, and it was more potent at alpha(4)beta(2)delta than at alpha(1)beta(2)gamma(2) receptors (the presumptive extrasynaptic and synaptic GABA(A)-R subtypes in VB neurons). We conclude that the extrasynaptic GABA(A)-Rs of thalamocortical neurons are sensitive to low concentrations of isoflurane. In view of the crucial role of the thalamus in sensory processing, sleep, and cognition, the modulation of these extrasynaptic GABA(A)-Rs by isoflurane may contribute to the sedation and hypnosis associated with low doses of this anesthetic agent.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1521-0103
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
324
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1127-35
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pubmed:meshHeading |
pubmed-meshheading:18094320-Animals,
pubmed-meshheading:18094320-Cell Line,
pubmed-meshheading:18094320-Dose-Response Relationship, Drug,
pubmed-meshheading:18094320-Humans,
pubmed-meshheading:18094320-Inhibitory Postsynaptic Potentials,
pubmed-meshheading:18094320-Isoflurane,
pubmed-meshheading:18094320-Mice,
pubmed-meshheading:18094320-Mice, Inbred C57BL,
pubmed-meshheading:18094320-Mice, Knockout,
pubmed-meshheading:18094320-Mice, Transgenic,
pubmed-meshheading:18094320-Receptors, GABA-A,
pubmed-meshheading:18094320-Synapses,
pubmed-meshheading:18094320-Thalamus
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pubmed:year |
2008
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pubmed:articleTitle |
Isoflurane is a potent modulator of extrasynaptic GABA(A) receptors in the thalamus.
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pubmed:affiliation |
Department of Anesthesiology, Weill Cornell Medical College, 1300 York Avenue, Room A-1050, New York, NY 10065, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, N.I.H., Extramural
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