Isoflurane inhibits multiple voltage-gated calcium currents in hippocampal pyramidal neurons

Anesthesiology. 1994 Jul;81(1):104-16. doi: 10.1097/00000542-199407000-00016.


Background: The mechanisms by which volatile anesthetics produce general anesthesia are unknown. Voltage-gated calcium currents in central neurons are potential target sites for general anesthetics because they are involved in the regulation of excitability and are essential for synaptic transmission.

Methods: Freshly isolated rat hippocampal pyramidal neurons were studied using the whole-cell patch clamp method. Calcium currents were isolated from other voltage-activated currents by blocking sodium and potassium channels. Calcium current subtypes were studied using the specific blockers nitrendipine and omega-conotoxin GVIA.

Results: Isoflurane inhibited multiple voltage-gated calcium currents in hippocampal neurons. Isoflurane inhibited both the high- and low-voltage-activated calcium current in a clinically relevant concentration range, giving half-maximal inhibition of the peak high-voltage-activated current (measured at current maximum) at about 2% gas phase concentration, and the sustained current (measured at the end of an 800-ms depolarization) at about 1%. Isoflurane also accelerated both components of the two-component exponential decay of the high-voltage-activated current. Studies using specific channel blockers showed that the calcium current contained contributions from T, L, N, and other channels, including probably P channels. Isoflurane inhibited all of these in clinically relevant concentrations, although detailed analysis of the effects on the individual channel types was not attempted.

Conclusions: Given the importance of calcium currents in the regulation of excitability in central neurons and the involvement of P and N channels in neurotransmitter release, this effect may represent an important action of volatile anesthetics in producing general anesthesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / classification
  • Calcium Channels / drug effects*
  • Calcium Channels / physiology*
  • Female
  • Ion Channel Gating / drug effects*
  • Ion Channel Gating / physiology
  • Isoflurane / pharmacology*
  • Kinetics
  • Male
  • Neurons / drug effects*
  • Neurons / physiology*
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / physiology*
  • Rats


  • Calcium Channel Blockers
  • Calcium Channels
  • Isoflurane