Attenuation of Gap-Junction-Mediated Signaling Facilitated Anesthetic Effect of Sevoflurane in the Central Nervous System of Rats

Eiji Masaki, Masahito Kawamura, Fusao Kato

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Accumulating evidence suggests that reduction of intrinsic excitability or synaptic excitation and/or an enhancement of synaptic inhibition underlie the general anesthetic condition. Besides chemical synapse, neurons could communicate with each other by electrical coupling via gap-junctions. We hypothesized that inhibition of cell-to-cell signaling through gap-junction in the central nervous system (CNS) is involved in the anesthetic mechanism of volatile anesthetics. The minimum alveolar concentration (MAC) of sevoflurane was measured after the intracerebroventricular (ICV) or intrathecal (IT) administration of carbenoxolone (CBX), a gap-junction inhibitor, in vivo. The spontaneous oscillation in membrane currents of locus coeruleus neurons that results from electrical coupling between neurons was also recorded from young rat pontine slices by the patch clamp method, and the effect of sevoflurane on this oscillation was examined in vitro. The ICV administration of CBX (125 and 250 μg/rat) significantly reduced the MAC of sevoflurane dose-dependently, whereas IT injection failed to inhibit the MAC. Sevoflurane at clinically relevant concentrations (0.1-0.5 mM) suppressed the spontaneous oscillation in membrane current concentration-dependently. These suppressions were significant at 0.5 mM with both amplitude and frequency. We suggest that suppression of gap-junction-mediated signaling in the CNS is involved in the anesthetic-induced immobilization by sevoflurane.

Original languageEnglish
Pages (from-to)647-652
Number of pages6
JournalAnesthesia and Analgesia
Volume98
Issue number3
DOIs
Publication statusPublished - 2004 Mar

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Fingerprint Dive into the research topics of 'Attenuation of Gap-Junction-Mediated Signaling Facilitated Anesthetic Effect of Sevoflurane in the Central Nervous System of Rats'. Together they form a unique fingerprint.

  • Cite this