Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila

• Published in: PLoS genetics 2016-01, Vol.12 (1), p.e1005784-e1005784
• Main Authors: Saras, Arunesh, Tanouye, Mark A
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Behavior; Calcium; Calcium - metabolism; Calcium channels; Calcium Channels - genetics; Dietary fiber; Disease Models, Animal; Drosophila; Drosophila Proteins - genetics; Epilepsy; Epilepsy - genetics; Epilepsy - pathology; Gene mutations; Genes; Genetic aspects; Health aspects; Humans; Insects; Mutation; Observations; Phenotype; Prevention; Seizures (Medicine); Seizures - genetics; Seizures - pathology; Temperature
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1005784

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.