Blockage of one class of potassium channel alters the effectiveness of halothane in a brain circuit of Drosophila
Abstract
At concentrations comparable to those used in the clinic, halothane has profound effects on a neuronal pathway devoted to the escape reflex of the fruit fly, Drosophila melanogaster. We studied the influence of the potassium channel that is encoded by the Shaker gene on the halothane sensitivity of this circuit. Shaker channels were specifically inactivated either by genetic means, using strains with two different severe Shaker mutations, or by pharmacologic means, using ingestion of millimolar concentrations of 4-aminopyridine. In all cases, halothane potency decreased substantially. To ensure that the genetic alteration was specific, both mutations were studied as stocks that had been repeatedly backcrossed to a control strain. The specificity of the pharmacologic inhibition was demonstrated by the fact that 4-aminopyridine had no effect on halothane potency in a Shaker mutant. Quantitative differences in the effects of channel inhibition between males and females suggested a sexual dimorphism in the functional brain anatomy of the reflex circuit. Implications Shaker channels are important elements during halothane inhibition of a specific reflex in Drosophila. Neurons that express these channels, which are irregularly distributed in the brain of flies, provide promising leads to identifying anesthetic-sensitive components.
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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 [56]
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- Authors
- Walcourt, A., Scott, R. L., & Nash, H. A.
- Affiliations
- National Institutes of Health (US)
- National Institute of Mental Health (US)
- Corresponding author
- Nash, Howard A.
- Venue
- Anesthesia & Analgesia
- Published
- 2001-02
- Volume
- 92
- Issue
- 2
- Pages
- 535-541
- ISSN
- 0003-2999 (ISSN-L)
- OpenAlex
- W2036537186
- Cited by
- 20
- References
- 27
- Citations by year
- 2026: 1 · 2023: 1 · 2019: 1 · 2017: 1 · 2015: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anesthesia & Analgesia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- halothane, Shaker potassium channel, anesthetic sensitivity, Drosophila melanogaster, escape reflex, 4-aminopyridine, sex differences
- MeSH terms
- Animals, Brain, Drosophila, Female, Halothane, Male, Mutation, Sex Characteristics, Potassium Channels, Anesthetics, Inhalation, Drosophila Proteins, Shaker Superfamily of Potassium Channels
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