Correction: Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila

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 para bss1 , 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 (cac TS2), a mutation of the Drosophila presynaptic Ca ++ channel α 1 subunit gene, is a particularly potent seizure-suppressor mutation, reverting seizure-like phenotypes for para bss1 and other BS mutants. Seizure-like phenotypes for para bss1 may be suppressed by as much as 90% in double mutant combinations with cac TS2. Unexpectedly, we find that para bss1 also reciprocally suppresses cac TS2 seizure-like phenotypes. The cac TS2 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 cac TS2 is ameliorated by 85% in double mutant combinations with para bss1. Author Summary Seizure disorders, such as epilepsy, are a serious health concern because of the large number of patients affected and a limited availability of treatment options. About 10% of the population will have at least one seizure during their lifetime, and 1% will experience persistent , recurrent epileptic seizures. Moreover, for about one-third of patients, epilepsy is intractable with seizures that are not controlled with any available drugs. Genetic seizure suppressors are modifier mutations that are capable of reverting seizure susceptibility to wild type levels when combined with seizure-prone mutants in double mutant individuals. Suppressors are valuable in providing an experimental approach that can provide insight into mechanisms underlying seizure susceptibility. Also, they identify novel gene products that may be targets for therapeutic drug development. In the present study we show that a severe seizure phenotype of the Drosophila paralytic bss1 (para bss1) mutant is 90% suppressed by the N-type calcium channel mutation cacophony TS2 (cac TS2). The effect of access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. …