Syntaxin1A-mediated Resistance and Hypersensitivity to Isoflurane in Drosophila melanogaster

Anesthesiology
Oressia ZaluckiB van Swinderen

Abstract

Recent evidence suggests that general anesthetics activate endogenous sleep pathways, yet this mechanism cannot explain the entirety of general anesthesia. General anesthetics could disrupt synaptic release processes, as previous work in Caenorhabditis elegans and in vitro cell preparations suggested a role for the soluble NSF attachment protein receptor protein, syntaxin1A, in mediating resistance to several general anesthetics. The authors questioned whether the syntaxin1A-mediated effects found in these reductionist systems reflected a common anesthetic mechanism distinct from sleep-related processes. Using the fruit fly model, Drosophila melanogaster, the authors investigated the relevance of syntaxin1A manipulations to general anesthesia. The authors used different behavioral and electrophysiological endpoints to test the effect of syntaxin1A mutations on sensitivity to isoflurane. The authors found two syntaxin1A mutations that confer opposite general anesthesia phenotypes: syxH3-C, a 14-amino acid deletion mutant, is resistant to isoflurane (n = 40 flies), and syxKARRAA, a strain with two amino acid substitutions, is hypersensitive to the drug (n = 40 flies). Crucially, these opposing effects are maintained across differ...Continue Reading

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Citations

Jul 2, 2016·Consciousness and Cognition·Oressia Zalucki, Bruno van Swinderen
May 10, 2017·Proceedings of the National Academy of Sciences of the United States of America·Brandon M BenselSusan P Gilbert
Nov 15, 2019·Alcoholism, Clinical and Experimental Research·Joydip Das
Feb 29, 2020·Current Neuropharmacology·Xuechao HaoCheng Zhou
Nov 22, 2017·British Journal of Anaesthesia·J R Sneyd

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