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PLoS Genet. 2016 Jan 15;12(1):e1005784. doi: 10.1371/journal.pgen.1005784. eCollection 2016 Jan.

Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila.

Author information

1
Department of Environmental Science, Policy and Management, Division of Organismal Biology, University of California Berkeley, Berkeley, California, United States of America.
2
Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America.

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.

PMID:
26771829
PMCID:
PMC4714812
DOI:
10.1371/journal.pgen.1005784
[Indexed for MEDLINE]
Free PMC Article

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