Nicholas P Franks

..The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors...

..2-A resolution. These results provide a structural basis for understanding the anesthetic inhibition of the enzyme, as well as an explanation for the ATP modulation of its anesthetic sensitivity...

..3. The targets which currently emerge as most important belong to an anaesthetic-sensitive superfamily of genetically related fast neurotransmitter-gated receptor channels present at central synapses...

..Xenon inhibits NMDA receptors by competing with glycine at the glycine-binding site. We test the hypothesis that inhibition of the NMDA receptor at the glycine site underlies xenon neuroprotection against hypoxia-ischemia...

..GABA(B) receptors on histaminergic neurons were dispensable for all behaviors examined. Synaptic inhibition of histaminergic cells by GABA(A) receptors, however, was essential for habituation to a novel environment...

..Therefore, the current study sought to investigate xenon's putative protective properties against anesthetic-induced neuronal apoptosis...

..We summarize recent in vitro and in vivo studies on the actions of helium and the other inert gases, and discuss their potential to be used as neuroprotective agents...

..These results imply a previously unexpected role for TASK-3 channels in the cellular mechanisms underlying these behaviors and suggest that endogenous modulators of these channels may regulate theta oscillations...

..Overall, our results support the idea that GABAergic anesthetics such as propofol exert their effects, at least in part, by modulating hypothalamic sleep pathways...

..The L159A mutation in LyTASK disrupts the stereoselective response to isoflurane while having no effect on the pH sensitivity of the channel, suggesting this critical amino acid may form part of an anesthetic binding site...

..In this review, we examine the evidence that anesthetic-induced loss of consciousness may be caused by actions on the neuronal pathways that produce natural sleep...

..The acyl azide etomidate may prove to be a useful new photolabel to identify anesthetic binding sites on the GABA(A) receptor or other putative targets...

..The "inert" gas xenon has been shown to be an effective neuroprotectant in a variety of in vitro and in vivo models of neuronal injury. We examined its neuroprotective properties in an in vitro model of traumatic brain injury...

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..7 +/- 0.8%). CONCLUSIONS: Although xenon does expand small air and oxygen bubbles, the extent to which this occurs under clinically relevant conditions of concentration and temperature is modest...

..These issues will be important when considering drug strategies designed to target extrasynaptic GABA(A) receptors in the treatment of sleep disorders and other neurological conditions...

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..Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial...

..Here we identify specific amino acids important for xenon binding to the NMDA receptor, with the aim of finding silent mutations that eliminate xenon binding but leave normal receptor function intact...

..If applied to humans, these data suggest that low (subanesthetic) concentrations of xenon in combination with mild hypothermia may provide a safe and effective therapy for perinatal asphyxia...

..Recent work suggests that the thalamus and the neuronal networks that regulate its activity are the key to understanding how anaesthetics cause loss of consciousness...

..These structures show anesthetic-protein interactions at the atomic level...

..However, the site of action of these agents on the NMDA receptor is unknown. The authors show that xenon and isoflurane compete for the binding of the coagonist glycine on the NMDA receptor NR1 subunit...