Syntaxin1A neomorphic mutations promote rapid recovery from isoflurane anesthesia in Drosophila melanogaster
Abstract
Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New: Background: Mutations in the presynaptic protein syntaxin1A modulate general anesthetic effects in vitro and in vivo. Coexpression of a truncated syntaxin1A protein confers resistance to volatile and intravenous anesthetics, suggesting a target mechanism distinct from postsynaptic inhibitory receptor processes. Hypothesizing that recovery from anesthesia may involve a presynaptic component, the authors tested whether syntaxin1A mutations facilitated recovery from isoflurane anesthesia in Drosophila melanogaster . Methods: A truncated syntaxin1A construct was expressed in Drosophila neurons. The authors compared effects on isoflurane induction versus recovery in syntaxin1A mutant animals by probing behavioral responses to mechanical stimuli. The authors also measured synaptic responses from the larval neuromuscular junction using sharp intracellular recordings, and performed Western blots to determine whether the truncated syntaxin1A is associated with presynaptic core complexes. Results: Drosophila expressing a truncated syntaxin1A (syx 227 , n = 40) were resistant to isoflurane induction for a behavioral responsiveness endpoint (ED50 0.30 ± 0.01% isoflurane, P < 0.001) compared with control (0.240 ± 0.002% isoflurane, n = 40). Recovery from isoflurane anesthesia was also faster, with syx 227 -expressing flies showing greater levels of responsiveness earlier in recovery (reaction proportion 0.66 ± 0.48, P < 0.001, n = 68) than controls (0.22 ± 0.42, n = 68 and 0.33 ± 0.48, n = 66). Measuring excitatory junction potentials of larvae coexpressing the truncated syntaxin1A protein showed a greater recovery of synaptic function, compared with controls (17.39 ± 3.19 mV and 10.29 ± 4.88 mV, P = 0.014, n = 8 for both). The resistance-promoting truncated syntaxin1A was not associated with presynaptic core complexes, in the presence or absence of isoflurane anesthesia. Conclusions: The same neomorphic syntaxin1A mutation that confers isoflurane resistance in cell culture and nematodes also produces isoflurane resistance in Drosophila . Resistance in Drosophila is, however, most evident at the level of recovery from anesthesia, suggesting that the syntaxin1A target affects anesthesia maintenance and recovery processes rather than induction. The absence of truncated syntaxin1A from the presynaptic complex suggests that the resistance-promoting effect of this molecule occurs before core complex formation.
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Recovery from anesthetic-induced modulation of presynaptic function plays an important role in exit from anesthetic states.
“Recovery from anesthetic-induced modulation of presynpatic function appears to play an even more important role in the exit from anesthetic states [81].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [81]
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- Authors
- Troup, M., Zalucki, O. H., Kottler, B. D., Karunanithi, S., Anggono, V., & van Swinderen, B.
- Affiliations
- Griffith University (AU)
- From the Queensland Brain Institute (M.T., O.H.Z., B.D.K., S.K., V.A., B.v.S.), School of Biomedical Sciences (O.H.Z.), and Clem Jones Centre for Ageing Dementia Research (V.A.), The University of Queensland, Brisbane, Queensland, Australia; School of Medical Science and Griffith Health Institute, Griffith University Gold Coast Campus, Queensland, Australia (S.K.).
- Venue
- Anesthesiology
- Published
- 2019-09
- Volume
- 131
- Issue
- 3
- Pages
- 555-568
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W2962855124
- Cited by
- 21
- References
- 51
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2021: 2 · 2020: 4 · 2019: 1
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- neomorphic mutations, isoflurane anesthesia, anesthesia recovery, presynaptic proteins, neuromuscular junction, synaptic function, Drosophila melanogaster, excitatory junction potentials, larval development
- MeSH terms
- Anesthesia Recovery Period, Animals, Drosophila melanogaster, Female, Isoflurane, Mutation, Neuromuscular Junction, Anesthetics, Inhalation, Drosophila Proteins, Qa-SNARE Proteins
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