Saifee_2011_Anesthesiology_115_1162

Reference

Title : A gain-of-function mutation in adenylate cyclase confers isoflurane resistance in Caenorhabditis elegans - Saifee_2011_Anesthesiology_115_1162
Author(s) : Saifee O , Metz LB , Nonet ML , Crowder CM
Ref : Anesthesiology , 115 :1162 , 2011
Abstract :

BACKGROUND: Volatile general anesthetics inhibit neurotransmitter release by a mechanism not fully understood. Genetic evidence in Caenorhabditis elegans has shown that a major mechanism of action of volatile anesthetics acting at clinical concentrations in this animal is presynaptic inhibition of neurotransmission. To define additional components of this presynaptic volatile anesthetic mechanism, C. elegans mutants isolated as phenotypic suppressors of a mutation in syntaxin, an essential component of the neurotransmitter release machinery, were screened for anesthetic sensitivity phenotypes. METHODS: Sensitivity to isoflurane concentrations was measured in locomotion assays on adult C. elegans. Sensitivity to the acetylcholinesterase inhibitor aldicarb was used as an assay for the global level of C. elegans acetylcholine release. Comparisons of isoflurane sensitivity (measured by the EC(5)(0)) were made by simultaneous curve-fitting and F test. RESULTS: Among the syntaxin suppressor mutants, js127 was the most isoflurane resistant, with an EC(5)(0) more than 3-fold that of wild type. Genetic mapping, sequencing, and transformation phenocopy showed that js127 was an allele of acy-1, which encodes an adenylate cyclase expressed throughout the C. elegans nervous system and in muscle. js127 behaved as a gain-of-function mutation in acy-1 and had increased concentrations of cyclic adenosine monophosphate. Testing of single and double mutants along with selective tissue expression of the js127 mutation revealed that acy-1 acts in neurons within a Galphas-PKA-UNC-13-dependent pathway to regulate behavior and isoflurane sensitivity. CONCLUSIONS: Activation of neuronal adenylate cyclase antagonizes isoflurane inhibition of locomotion in C. elegans.

PubMedSearch : Saifee_2011_Anesthesiology_115_1162
PubMedID: 22024713

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Citations formats

Saifee O, Metz LB, Nonet ML, Crowder CM (2011)
A gain-of-function mutation in adenylate cyclase confers isoflurane resistance in Caenorhabditis elegans
Anesthesiology 115 :1162

Saifee O, Metz LB, Nonet ML, Crowder CM (2011)
Anesthesiology 115 :1162