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Cited by 39Ion channel regulation and functionAnesthesia and Sedative AgentsNicotinic Acetylcholine Receptors Study

Analysis of anesthetic action on the potassium channels of the Shaker mutant of Drosophila

TINKLENBERG, JULIE A, SEGAL, IRA S., TIANZHI, GUO, MAZE, MERVYN·1991·Annals of the New York Academy of Sciences
DOI 10.1111/j.1749-6632.1991.tb33884.x
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Abstract

Recent evidence suggest that exposure to volatile anesthetic agents causes a change in conductance through an undelineated potassium channel. With recently developed genetic and molecular techniques the Drosophila melanogaster (D.m.) genome can be manipulated to study the role that potassium ion channel function plays in anesthetic action. The IA potassium channel is encoded by the Shaker (Sh) locus on the X chromosome of D.m. Because this channel may be one of those involved in volatile anesthetic action, we tested the sensitivity to isoflurane in three Shaker strains with different degrees of dysfunctional IA conductance (Shnull greater than ShKS133 greater than Sh5). Anesthetic sensitivity was also examined in mutant strains of D.m. which express abnormalities either in other potassium channel conductances (eag, slo) or other ion conductances (para). The normally conducting wild type served as the control. Two-day-old adult D.m. were stimulated with a heat source during exposure to the volatile anesthetic isoflurane, and the number moving in response to the noxious stimulus was noted. After testing the Shaker and control strains at no fewer than 13 concentrations, the IC50S (isoflurane concentration in percent vol/vol at which 50% of the flies did not respond to the heat stimulus) were derived. The IC50 values for Sh 5 (0.89), Sh133 (1.29), and Shnull (1.37) were significantly different from the wild type (0.56). The rank order of insensitivity of these Shaker mutants corresponded to the extent of the alteration in IA conductance as established by previous studies in these mutants. Neither eag (0.66), para (0.48), nor slo (0.63) differed significantly from the wild type. These data suggest that the IA potassium channel plays a role in volatile anesthetic action.

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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 [55]

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Authors
TINKLENBERG, J. A., SEGAL, I. S., TIANZHI, G., & MAZE, M.
Affiliations
  • Stanford Medicine (US)
  • University of Minnesota (US)
  • Stanford University (US)
Corresponding author
SEGAL, IRA S.
ORCID
MAZE, MERVYN
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
1991-06
Volume
625
Issue
1
Pages
532-532
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1111/j.1749-6632.1991.tb33884.x
OpenAlex
W1990470989
Cited by
39
References
22
Citations by year
2023: 1 · 2019: 1 · 2018: 2 · 2015: 2 · 2014: 1 · 2013: 1
FWCI
0.53
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5678 d)
Locations
  • Annals of the New York Academy of Sciences (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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
volatile anesthetics, isoflurane, Shaker potassium channel, Drosophila melanogaster, anesthetic sensitivity, EAG potassium channels
MeSH terms
Animals, Drosophila melanogaster, Hot Temperature, Isoflurane, Mutation, X Chromosome, Potassium Channels

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