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General anesthetics have been used in clinical practice since the middle of the XIXth century, but their molecular mechanisms of action on the nervous system remains poorly understood. The main targets of most inhalational anesthetic are pentameric ligand-gated ion channels such as inhibitory GABAA (-amino-butyric acid) receptors whose activity is potentiated by general anesthetics. However, the main targets of gaseous anesthetics like xenon or nitrous oxide are excitatory NMDA (N-methyl-D-aspartate) receptors and nicotinic acetylcholine receptors whose activity is inhibited by gaseous anesthetics (Campagna et al., 2003; Franks, 2008). The use of gaseous anesthetics became widely applicable in the nineteen-fifties, nitrous oxide being often administrated in complement of halogenated anesthetics. Xenon anesthetic properties have been described by Cullen in 1951 (Cullen et al., 1951), and is used in anesthesia since mid-2000 (Sanders et al., 2004; Sanders et al., 2005) in spite of its excessive cost, a major obstacle to its widespread use (Kennedy et al., 1992). Anesthesia is a complex process that refers to several physiologically altered functions. Early stages of anesthesia such as amnesia and hypnosis required anesthetic concentrations lower than those required to produce deep sedation and reduction of motor and automomic responses to noxious stimuli (Campagna et al., 2003). Scales that assess the in-vivo potency of inhaled anesthetics in humans are based on the minimum alveolar anesthetic concentrations (MAC) that are associated with well-defined behavioural endpoints. Following this, MAC-awake defines the MAC that induces the first stages of anesthesia such as amnesia and hypnosis, and MAC-immobility defines the MAC that produces deep sedation and suppresses movement in response to a noxious stimuli. Anesthesia mechanisms were for a long time though to be mediated by non-specific membranous perturbation (Trudell, 1977). This membranous theory was based on the Meyer-Overton rule that showed an almost perfect relationship between the anesthetic property of a chemical compound and its solubility in olive oil or benzene. However, more and more exceptions were found to the Meyer-Overton rule such as the non-immobilizers

Protein-Noble Gas Interactions Investigated by Crystallography on Three Enzymes - Implication on Anesthesia and Neuroprotection Mechanisms