Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer properties Academic Article uri icon


MeSH Major

  • Isoflurane
  • Lipid Bilayers
  • Sodium
  • Voltage-Gated Sodium Channels


  • Although general anesthetics are clinically important and widely used, their molecular mechanisms of action remain poorly understood. Volatile anesthetics such as isoflurane (ISO) are thought to alter neuronal function by depressing excitatory and facilitating inhibitory neurotransmission through direct interactions with specific protein targets, including voltage-gated sodium channels (Na(v)). Many anesthetics alter lipid bilayer properties, suggesting that ion channel function might also be altered indirectly through effects on the lipid bilayer. We compared the effects of ISO and of a series of fluorobenzene (FB) model volatile anesthetics on Na(v) function and lipid bilayer properties. We examined the effects of these agents on Na(v) in neuronal cells using whole-cell electrophysiology, and on lipid bilayer properties using a gramicidin-based fluorescence assay, which is a functional assay for detecting changes in lipid bilayer properties sensed by a bilayer-spanning ion channel. At clinically relevant concentrations (defined by the minimum alveolar concentration), both the FBs and ISO produced prepulse-dependent inhibition of Na(v) and shifted the voltage dependence of inactivation toward more hyperpolarized potentials without affecting lipid bilayer properties, as sensed by gramicidin channels. Only at supra-anesthetic (toxic) concentrations did ISO alter lipid bilayer properties. These results suggest that clinically relevant concentrations of volatile anesthetics alter Na(v) function through direct interactions with the channel protein with little, if any, contribution from changes in bulk lipid bilayer properties. Our findings further suggest that changes in lipid bilayer properties are not involved in clinical anesthesia.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4242807

Digital Object Identifier (DOI)

  • 10.1085/jgp.201411172

PubMed ID

  • 25385786

Additional Document Info

start page

  • 545

end page

  • 60


  • 144


  • 6