Analysis of volatile anestheics: involvement of intracellular signaling and neural transmission

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Suppression of movement during induction of anesthesia is mediated through subcortical structures. We studied the effects of a brief 5-min application of a clinically relevant concentration of sevoflurane on the electrophysiological activities of the medium spiny neurons of the stratum in brain slice preparations, using a whole-cell patch-clamp technique. We found that sevoflurane depressed the peak, as well as the net, charge transfer of intrastriatally evoked inhibitory postsynaptic currents much more strongly than those of excitatory postsynaptic currents. And this inhibition was accompanied by an elevated paired-pulse ratio. The strong suppression of eIPSCs paralleled a significant suppression of the spontaneous EPSCs. These results suggest that, in contrast to its effects on other brain structures, sevoflurane shifts the balance between synaptic excitation and inhibition in the direction of excitation in the stratum, thereby causing involuntary movements during induction of anesthesia by sevoflurane.And, Sevoflurane has been shown to enhance two types of GABAergic inhibition: a synaptic form (phasic inhibition) regulating neural excitability via the activation of postsynaptic GABAA receptors by intermittent GABA release from presynaptic terminals；and a persistent tonic form (tonic inhibition) generated by continuous activation of extrasynaptic GABAA receptors by low concentrations of ambient GABA.