Differential Inhibition of Neuronal Sodium Channel Subtypes by the General Anesthetic Isoflurane Academic Article uri icon


MeSH Major

  • Actins
  • Anesthetics, Inhalation
  • Dendritic Spines
  • Hippocampus
  • Isoflurane


  • Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics. Volatile anesthetics depress neurotransmitter release in a brain region- and neurotransmitter-selective manner by unclear mechanisms. Voltage-gated sodium channels (Navs), which are coupled to synaptic vesicle exocytosis, are inhibited by volatile anesthetics through reduction of peak current and modulation of gating. Subtype-selective effects of anesthetics on Nav might contribute to observed neurotransmitter-selective anesthetic effects on release. We analyzed anesthetic effects on Na+ currents mediated by the principal neuronal Nav subtypes Nav1.1, Nav1.2, and Nav1.6 heterologously expressed in ND7/23 neuroblastoma cells using whole-cell patch-clamp electrophysiology. Isoflurane at clinically relevant concentrations induced a hyperpolarizing shift in the voltage dependence of steady-state inactivation and slowed recovery from fast inactivation in all three Nav subtypes, with the voltage of half-maximal steady-state inactivation significantly more positive for Nav1.1 (-49.7 ± 3.9 mV) than for Nav1.2 (-57.5 ± 1.2 mV) or Nav1.6 (-58.0 ± 3.8 mV). Isoflurane significantly inhibited peak Na+ current (INa) in a voltage-dependent manner: at a physiologically relevant holding potential of -70 mV, isoflurane inhibited peak INa of Nav1.2 (16.5% ± 5.5%) and Nav1.6 (18.0% ± 7.8%), but not of Nav1.1 (1.2% ± 0.8%). Since Nav subtypes are differentially expressed both between neuronal types and within neurons, greater inhibition of Nav1.2 and Nav1.6 compared with Nav1.1 could contribute to neurotransmitter-selective effects of isoflurane on synaptic transmission.

publication date

  • May 2019



  • Academic Article



  • eng

PubMed Central ID

  • PMC6439525

Digital Object Identifier (DOI)

  • 10.1124/jpet.118.254938

PubMed ID

  • 30792243

Additional Document Info

start page

  • 200

end page

  • 211


  • 369


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