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→Mechanisms of Anesthesia
*Based on 30 years of in vitro studies (n>300), most anesthetics exhibit similar potency across a range of receptors. Most receptors are non-selective for ligands. What this paper addresses but doesn't answer is whether the receptors are present at the correct locations and necessary to the anesthetic behavioral response.
*Based on 30 years of in vitro studies (n>300), most anesthetics exhibit similar potency across a range of receptors. Most receptors are non-selective for ligands. What this paper addresses but doesn't answer is whether the receptors are present at the correct locations and necessary to the anesthetic behavioral response.
*Some anesthetics ('''ketamine, dexmedetomidine, etomidate, benzos''') are fairly selective, but are rarely used as sole anesthetics.
*Some anesthetics ('''ketamine, dexmedetomidine, etomidate, benzos''') are fairly selective, but are rarely used as sole anesthetics.
*[https://journals.lww.com/anesthesia-analgesia/fulltext/10.1213/ane.0000000000007888~are-gabaergic-agents-really-so-selective-for-gaba 2026 A&A paper] argues that classifying anesthetics as, say, GABAergic vs. NMDAergic is misleading. Propofol for instance actually has higher potency at the α4β2 nAChR and HCN1 receptors than at the "classic" GABA<sub>A</sub>R receptor.
*[https://scholar.googleusercontent.com/scholar.bib?q=info:dK96wvRnWFAJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixESwUs:ACTRDVEAAAAAasUU2UsAEqSgPmvYJRTMHcZKb4s&scisig=ACTRDVEAAAAAasUU2a34RqVYzDaWRdbVsL76Mk4&scisf=4&ct=citation&cd=-1&hl=en 2026 A&A paper] argues that classifying anesthetics as, say, GABAergic vs. NMDAergic is misleading. Propofol for instance actually has higher potency at the α4β2 nAChR and HCN1 receptors than at the "classic" GABA<sub>A</sub>R receptor.
*What if you found pharmacological inhibitors that were receptor specific and gave them together with "promiscuous" anesthetics. For instance, is propofol equally effective when given with a specific HCN1 receptor inhibitor? What about a GABA<sub>A</sub>R inhibitor? Could you do optogenetic location-specific receptor knockdowns?
*What if you found pharmacological inhibitors that were receptor specific and gave them together with "promiscuous" anesthetics. For instance, is propofol equally effective when given with a specific HCN1 receptor inhibitor? What about a GABA<sub>A</sub>R inhibitor? Could you do optogenetic location-specific receptor knockdowns?
*Hamilton has a gap junction (network of gap junctions?) and some specific neurons that he think are a conserved mechanism of anesthesia. He wants to test this by doing a screen of a bunch of different anesthetics in WT and KO worms with a behavioral screening assay. He has a behavior rig that basically automatically records swimming speed. He wants to look for the EC50 of various anesthetics and see if that number is shifted with KO or KD of different gap junctions.
*Hamilton has a gap junction (network of gap junctions?) and some specific neurons that he think are a conserved mechanism of anesthesia. He wants to test this by doing a screen of a bunch of different anesthetics in WT and KO worms with a behavioral screening assay. He has a behavior rig that basically automatically records swimming speed. He wants to look for the EC50 of various anesthetics and see if that number is shifted with KO or KD of different gap junctions.