Syntaxin1A-mediated resistance and hypersensitivity to isoflurane in Drosophila melanogaster

Zalucki, Oressia H., Menon, Hareesh, Kottler, Benjamin, Faville, Richard, Day, Rebecca, Bademosi, Adekunle T., Lavidis, Nickolas, Karunanithi, Shanker and van Swinderen, Bruno (2015) Syntaxin1A-mediated resistance and hypersensitivity to isoflurane in Drosophila melanogaster. Anesthesiology, 122 5: 1060-1074. doi:10.1097/ALN.0000000000000629

Author Zalucki, Oressia H.
Menon, Hareesh
Kottler, Benjamin
Faville, Richard
Day, Rebecca
Bademosi, Adekunle T.
Lavidis, Nickolas
Karunanithi, Shanker
van Swinderen, Bruno
Title Syntaxin1A-mediated resistance and hypersensitivity to isoflurane in Drosophila melanogaster
Journal name Anesthesiology   Check publisher's open access policy
ISSN 0003-3022
Publication date 2015-05-01
Year available 2015
Sub-type Article (original research)
DOI 10.1097/ALN.0000000000000629
Open Access Status
Volume 122
Issue 5
Start page 1060
End page 1074
Total pages 15
Place of publication Philadelphia, PA United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Background: 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.

Methods: 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.

Results: 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 different behavioral endpoints and life stages. The authors determined the isoflurane sensitivity of syxH3-C at the larval neuromuscular junction to assess effects on synaptic release. The authors find that although isoflurane slightly attenuates synaptic release in wild-type animals (n = 8), syxH3-C preserves synaptic release in the presence of isoflurane (n = 8).

Conclusion: The study results are evidence that volatile general anesthetics target synaptic release mechanisms; in addition to first activating sleep pathways, a major consequence of these drugs may be to decrease the efficacy of neurotransmission.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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