Volatile anesthetic action in a computational model of the thalamic reticular nucleus

Allan Gottschalk, Sam A. Miotke

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Although volatile anesthetics (VAs) modulate the activity of multiple ion channels, the process whereby one or more of these effects are integrated to produce components of the general anesthetic state remains enigmatic. Computer models offer the opportunity to examine systems level effects of VA action at one or more sites. Motivated by the role of the thalamus in consciousness and sensory processing, a computational model of the thalamic reticular nucleus was used to determine the collective impact on model behavior of VA action at multiple sites. METHODS: A computational model of the thalamic reticular nucleus was modified to permit VA modulation of its ion channels. Isobolographic analysis was used to determine how multiple sites interact. RESULTS: VA modulation of either T-type Ca channels or γ-aminobutyric acid type A receptors led to increased network synchrony. VA modulation of both further increased network synchronization. VA-induced decrements in Ca current permitted greater impact of inhibitory currents on membrane potential, but at higher VA concentrations the decrease in Ca current led to a decreased number of spikes in the burst generating the inhibitory signal. MAC-awake (the minimum alveolar concentration at which 50% of subjects will recover consciousness) concentrations of both isoflurane and halothane led to similar levels of network synchrony in the model. CONCLUSIONS: Relatively modest VA effects at both T-type Ca channels and γ-aminobutyric acid type A receptors can substantially alter network behavior in a computational model of a thalamic nucleus. The similarity of network behavior at MAC-awake concentrations of different VAs is consistent with a contribution of the thalamus to VA-induced unconsciousness through action at these channels.

Original languageEnglish (US)
Pages (from-to)996-1010
Number of pages15
JournalAnesthesiology
Volume110
Issue number5
DOIs
StatePublished - May 2009

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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