title: Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila.
abstract: Bang sensitive (BS) Drosophila mutants display characteristic seizure-like phenotypes resembling, in some aspects, those of human seizure disorders such as epilepsy. The BS mutant parabss1, caused by a gain-of-function mutation of the voltage-gated Na+ channel gene, is extremely seizure-sensitive with phenotypes that have proven difficult to ameliorate by anti-epileptic drug feeding or by seizure-suppressor mutation. It has been presented as a model for intractable human epilepsy. Here we show that cacophony (cacTS2), a mutation of the Drosophila presynaptic Ca++ channel α1 subunit gene, is a particularly potent seizure-suppressor mutation, reverting seizure-like phenotypes for parabss1 and other BS mutants. Seizure-like phenotypes for parabss1 may be suppressed by as much as 90% in double mutant combinations with cacTS2. Unexpectedly, we find that parabss1 also reciprocally suppresses cacTS2 seizure-like phenotypes. The cacTS2 mutant displays these seizure-like behaviors and spontaneous high-frequency action potential firing transiently after exposure to high temperature. We find that this seizure-like behavior in cacTS2 is ameliorated by 85% in double mutant combinations with parabss1.
authors.affiliation: Department of Environmental Science, Policy and Management, Division of Organismal Biology, University of California Berkeley, Berkeley, California, United States of America.
authors.forename: Arunesh
authors.initials: A
authors.lastname: Saras
authors.affiliation: Department of Environmental Science, Policy and Management, Division of Organismal Biology, University of California Berkeley, Berkeley, California, United States of America.|Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tanouye
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics*; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012640:Seizures / Q000235:genetics* / Q000473:pathology
chemical_list: D015220:Calcium Channels; D029721:Drosophila Proteins; C472405:cac protein, Drosophila; D002118:Calcium