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Keywords:

  • Axon;
  • bouton;
  • synapse;
  • calcium;
  • anaesthetic;
  • pentobarbitone;
  • procaine;
  • calcium transient;
  • hippocampus
  • Although barbiturates, like other general anaesthetics, depress excitatory synaptic transmission in the central nervous system (CNS), the underlying cellular mechanisms remain unresolved. They may increase the likelihood that an action potential will fail to invade every branch of the axonal arbour, thereby decreasing the synaptic drive to the postsynaptic neurons. Alternatively, they may inhibit calcium entry into the presynaptic terminals, thus reducing transmitter release.

  • To resolve these issues, we have used two-photon microscopy to monitor calcium transients evoked by action potentials in axons, axonal varicosities (synaptic boutons) and fine axon collaterals of hippocampal CA1 neurons.

  • Pentobarbitone (75–300 μM) did not block the invasion of the axonal arbour or the synaptic boutons, but it did reduce the amplitude of the calcium transients recorded from the axons in a concentration-dependent manner. At 150 μM, pentobarbitone reduced the transients to 78±4% of the control.

  • Pentobarbitone depressed the calcium transients recorded from the synaptic boutons in a concentration-dependent manner. When 150 μM pentobarbitone was applied, the calcium transients recorded from the boutons were 53±3% of the control. This concentration of pentobarbitone also reduced the amplitude and frequency of the spontaneous excitatory postsynaptic potentials to 54±4 and 42±17% of the control, respectively.

  • The local anaesthetic procaine (500 μM) had no significant effect on action potential invasion of axon collaterals, even though it reduced the action potential amplitude by 25%.

  • This data are consistent with the notion that the pentobarbitone-induced depression of presynaptic calcium transients contributes to its depressant effect on excitatory synaptic transmission in the CNS.

British Journal of Pharmacology (2003) 140, 971–979. doi:10.1038/sj.bjp.0705519