A tail-flick assay for anesthesia in Drosophila melanogaster has been improved and refined. We established a protocol that yields reliable measures of anesthetic potency that under conditions when the fruit fly has equilibrated with the anesthetic gas. The assay has been used to refine the genetic map location for two alleles of a gene that affects the response to anesthetics and to provide the first evidence for genetic loci that interact with a second anesthesia gene. The issue of uniformity of anesthetic action has been analyzed by comparing the effects of genetic variations on the effectiveness of different general anesthetics. The results provide evidence for the existence of subgroups of anesthetics that have related action at their target(s) and they place severe limits on the degree to which different anesthetics can have identical action at a single target. The importance of ion channels has been investigated by determining the alteration in general anesthesia caused by mutations in the components of these structures. The results show that ion channels impinge on the anesthetic pathway in non-trivial ways. Comparison of anesthetic effects in two different assays suggests that challenge by anesthetics can delineate the importance of particular ion channels for different behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002228-08
Application #
3781366
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Burg, E D; Langan, S T; Nash, H A (2013) Drosophila social clustering is disrupted by anesthetics and in narrow abdomen ion channel mutants. Genes Brain Behav 12:338-47
Peabody, Nathan C; Pohl, Jascha B; Diao, Fengqiu et al. (2009) Characterization of the decision network for wing expansion in Drosophila using targeted expression of the TRPM8 channel. J Neurosci 29:3343-53
Sandstrom, David J (2008) Isoflurane reduces excitability of Drosophila larval motoneurons by activating a hyperpolarizing leak conductance. Anesthesiology 108:434-46
Cheng, Yuzhong; Nash, Howard A (2008) Visual mutations reveal opposing effects of illumination on arousal in Drosophila. Genetics 178:2413-6
Cheng, Yuzhong; Nash, Howard A (2007) Drosophila TRP channels require a protein with a distinctive motif encoded by the inaF locus. Proc Natl Acad Sci U S A 104:17730-4
Humphrey, John A; Hamming, Kevin S; Thacker, Colin M et al. (2007) A putative cation channel and its novel regulator: cross-species conservation of effects on general anesthesia. Curr Biol 17:624-9
Yu, James X; Guan, Zhonghui; Nash, Howard A (2006) The mushroom body defect gene product is an essential component of the meiosis II spindle apparatus in Drosophila oocytes. Genetics 173:243-53
Rajaram, Shantadurga; Scott, Robert L; Nash, Howard A (2005) Retrograde signaling from the brain to the retina modulates the termination of the light response in Drosophila. Proc Natl Acad Sci U S A 102:17840-5
Sandstrom, David J; Nash, Howard (2004) Drug targets: turning the channel (on) for sedation. Curr Biol 14:R185-6
Sandstrom, David J (2004) Isoflurane depresses glutamate release by reducing neuronal excitability at the Drosophila neuromuscular junction. J Physiol 558:489-502

Showing the most recent 10 out of 17 publications