[How far has our understanding of mechanisms of general anesthesia advanced?: preface and comments]

Although the great advance has been made in clinical anesthesia practice, the fundamental mechanisms of anesthetic action still remain to be an unsolved mystery. The early lipid membrane theory based on Meyer and Overton's law was taken over by the proteo-centric view of mechanism. Studies at the molecular and cellular level have shown that anesthetics act on a wide rage of functional proteins, including ligand-gated ion channels (GABA, glycine, NMDA receptors), two pore domain K channels and other ion channels. The effects on the individual channels, however, differ among various types of anesthetics. Elucidating how anesthetics work on the neuronal pathways is important to find the link between the molecular studies and in vivo action of anesthetics. Anesthesia disrupts the linkages between cortical and thalamic neurons and those among the cortical neurons, as well as depression and activation of the arousal and sleep nuclei, respectively. Functional brain imaging has revealed the global effects of general anesthetics on the human brain. Taken together, the disruption of thalamocortical connectivity and the integrative properties of the cerebral cortex might be an essential common feature of anesthetic action.