Increased volatile anesthetic requirement in short-sleeping Drosophila mutants
Open accessAbstract
Background: Anesthesia and sleep share physiologic and behavioral similarities. The anesthetic requirement of the recently identified Drosophila mutant minisleeper and other Drosophila mutants was investigated. Methods: Sleep and wakefulness were determined by measuring activity of individual wild-type and mutant flies. Based on the response of the flies at different concentrations of the volatile anesthetics isoflurane and sevoflurane, concentration-response curves were generated and EC50 values were calculated. Results: The average amount of daily sleep in wild-type Drosophila (n = 64) was 965 +/- 15 min, and 1,022 +/- 29 in Na[har](P > 0.05; n = 32) (mean +/- SEM, all P compared to wild-type and other shaker alleles). Sh flies slept 584 +/- 13 min (n = 64, P < 0.01), Sh flies 412 +/- 22 min (n = 32, P < 0.01), and Sh flies 782 +/- 25 min (n = 32, P < 0.01). The EC50 values for isoflurane were 0.706 (95% CI 0.649 to 0.764, n = 661) and for sevoflurane 1.298 (1.180 to 1.416, n = 522) in wild-type Drosophila; 1.599 (1.527 to 1.671, n = 308) and 2.329 (2.177 to 2.482, n = 282) in Sh, 1.306 (1.212 to 1.400, n = 393) and 2.013 (1.868 to 2.158, n = 550) in Sh, 0.957 (0.860 to 1.054, n = 297) and 1.619 (1.508 to 1.731, n = 386) in Sh, and 0.6154 (0.581 to 0.649, n = 360; P < 0.05) and 0.9339 (0.823 to 1.041, n = 274) in Na[har], respectively (all P < 0.01). Conclusions: A single-gene mutation in Drosophila that causes an extreme reduction in daily sleep is responsible for a significant increase in the requirement of volatile anesthetics. This suggests that a single gene mutation affects both sleep behavior and anesthesia and sedation.
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Shaker potassium channel mutants in fruit flies show a 25-50% right-shift in volatile anesthetic dose-response and can exit anesthesia at doses where wild-type siblings remain anesthetized and immobile.
“These flies display a resistant, right-shift in their volatile anesthetic dose-response curves of roughly 25%−50% but, more remarkably, are capable of exiting states of anesthesia at doses in which their wild-type siblings remain fully anesthetized and immobile [54–57].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [57]
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- Authors
- Weber, B., Schaper, C., Bushey, D., Rohlfs, M., Steinfath, M., Tononi, G., Cirelli, C., Scholz, J., & Bein, B.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Anesthesiology
- Published
- 2009-02-01
- Volume
- 110
- Issue
- 2
- Pages
- 313-316
- ISSN
- 0003-3022 (ISSN-L)
- PMC
- PMC2776714
- OpenAlex
- W1984978431
- Cited by
- 26
- References
- 30
- Citations by year
- 2024: 2 · 2021: 1 · 2019: 3 · 2018: 4 · 2017: 1 · 2014: 2 · 2013: 4 · 2012: 3
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DP1OD000579)
- National Institute of General Medical Sciences (R01GM075315)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- volatile anesthetics, anesthetic requirements, sleep, short sleep duration, isoflurane, sevoflurane, EC50, Drosophila, sleep-wake behavior
- MeSH terms
- Alleles, Animals, Dose-Response Relationship, Drug, Drosophila, Female, Isoflurane, Male, Motor Activity, Mutation, Sleep, Anesthetics, Inhalation
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