Cholinergic modulation of sevoflurane potency in cortical and spinal networks in vitro.

Abstract:

BACKGROUND:Victims of organophosphate intoxication with cholinergic crisis may have need for sedation and anesthesia, but little is known about how anesthetics work in these patients. Recent studies suggest that cholinergic stimulation impairs gamma-aminobutyric acid type A (GABAA) receptor function. Because GABAA receptors are major targets of general anesthetics, the authors investigated interactions between acetylcholine and sevoflurane in spinal and cortical networks. METHODS:Cultured spinal and cortical tissue slices were obtained from embryonic and newborn mice. Drug effects were assessed by extracellular voltage recordings of spontaneous action potential activity. RESULTS:Sevoflurane caused a concentration-dependent decrease in spontaneous action potential firing in spinal (EC50=0.17+/-0.02 mM) and cortical (EC50=0.29+/-0.01 mM) slices. Acetylcholine elevated neuronal excitation in both preparations and diminished the potency of sevoflurane in reducing action potential firing in cortical but not in spinal slices. This brain region-specific decrease in sevoflurane potency was mimicked by the specific GABAA receptor antagonist bicuculline, suggesting that (1) GABAA receptors are major molecular targets for sevoflurane in the cortex but not in the spinal cord and (2) acetylcholine impairs the efficacy of GABAA receptor-mediated inhibition. The latter hypothesis was supported by the finding that acetylcholine reduced the potency of etomidate in depressing cortical and spinal neurons. CONCLUSIONS:The authors raise the question whether cholinergic overstimulation decreases the efficacy of GABAA receptor function in patients with organophosphate intoxication, thereby compromising anesthetic effects that are mediated predominantly via these receptors such as sedation and hypnosis.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Grasshoff C,Drexler B,Hentschke H,Thiermann H,Antkowiak B

doi

10.1097/01.anes.0000267598.65120.f2

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

1147-55

issue

6

eissn

0003-3022

issn

1528-1175

pii

00000542-200706000-00015

journal_volume

106

pub_type

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