Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila

PLoS Genetics
Arunesh Saras, Mark A Tanouye

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.

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References

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Citations

Sep 21, 2016·Annals of Clinical and Translational Neurology·Salleh N EhaidebJ Robert Manak
Jul 13, 2018·Frontiers in Pharmacology·Muhammad Faiz Johan AriefMohd Farooq Shaikh
Aug 26, 2016·G3 : Genes - Genomes - Genetics·Arunesh Saras, Mark A Tanouye
Sep 10, 2020·International Journal of Molecular Sciences·Akari TakaiTomohiro Chiyonobu
Feb 24, 2021·Disease Models & Mechanisms·Grant F MarshallCatherine M Abbott
Apr 20, 2021·Neuroscience Insights·Kristin M Scaplen, Emily Petruccelli

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