Department of Anesthesiology

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Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABA(A) receptor chloride channels.

TitlePropofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABA(A) receptor chloride channels.
Publication TypeJournal Article
Year of Publication2005
AuthorsYing S-W, Goldstein PA
JournalMol Pain
Volume1
Pagination2
Date Published2005
ISSN1744-8069
KeywordsAnesthetics, Intravenous, Animals, Chloride Channels, Drug Synergism, Excitatory Postsynaptic Potentials, Mice, Mice, Inbred C57BL, Neural Inhibition, Neurons, Propofol, Receptors, GABA-A, Synapses
Abstract

Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli. However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal summation and action potential firing were evoked in VB neurons by electrical stimulation of corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 - 3 microM) suppressed temporal summation and spike firing in a concentration-dependent manner. The thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and input resistance, indicating that a shunting mechanism was involved. The propofol-mediated thalamocortical suppression could be blocked by a GABAA receptor antagonist or chloride channel blocker, suggesting that postsynaptic GABAA receptors in VB neurons were involved in the shunting inhibition. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly increased amplitude, decay time, and charge transfer of GABAA IPSCs. The results demonstrated that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant concentrations is primarily mediated through the potentiation of the GABAA receptor chloride channel-mediated conductance, and such inhibition may contribute to the impaired thalamic responses to sensory stimuli seen during propofol-induced anesthesia.

DOI10.1186/1744-8069-1-2
Alternate JournalMol Pain
PubMed ID15813991
PubMed Central IDPMC1074352
Grant ListGM66840 / GM / NIGMS NIH HHS / United States
R01 GM066840-01A1 / GM / NIGMS NIH HHS / United States