Article

A genetic study of the anesthetic response: mutants of Drosophila melanogaster altered in sensitivity to halothane.

Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/1990; 87(21):8632-6. DOI: 10.1073/pnas.87.21.8632
Source: PubMed

ABSTRACT In an attempt to identify genes that control or encode the targets of general anesthetics, we have chemically mutagenized fruit flies and selected four lines that show an abnormal response to the volatile anesthetic halothane. Specifically, about 2-fold higher concentrations of halothane are required to induce the loss of motor control in the mutant flies. Fine mapping of two isolates indicates that they alter a previously uncharacterized gene of Drosophila. In the absence of anesthetics, these mutants display alterations of behavior that imply changes in the adult and the larval neuromuscular system.

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    • "In flies, volatile organic solvent anesthetics, such as halothane and isoflurane, induce a state of sedation characterized by complete immobility and the loss of the ability to maintain postural control or respond to stimuli (Allada and Nash, 1993; Krishnan and Nash, 1990). Less-volatile organic solvents, such as ethanol and benzyl alcohol, have been shown to induce a biphasic response characterized by a brief initial increase in locomotor activity followed by sedation (Cowmeadow et al., 2005; Ghezzi et al., 2004; Moore et al., 1998; Parr et al., 2001; Scholz et al., 2000). "
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    • "In addition to the defect in behavioral circadian rhythms, the Drosophila mutant also displays other phenotypes, including narrow abdomen and altered sensitivity to anesthetics (Krishnan and Nash, 1990; Mir et al., 1997; van Swinderen, 2006). The complexity of the phenotypes suggests additional physiological roles of the NALCN channel. "
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    • "na mutants were discovered on the basis of their abdominal phenotype as well as altered responses to the general anesthetic halothane (Krishnan and Nash, 1990; Leibovitch et al., 1995). The na mutant alleles na 1 and na har are strong loss-of-function alleles with very low or undetectable levels of NA (Krishnan and Nash, 1990; Nash et al., 2002). na mutants fail to robustly increase activity in anticipation of LD transitions and in response to lights on. "
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