Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / genetics*
  • Disease Models, Animal
  • Drosophila Proteins / genetics*
  • Epilepsy / genetics*
  • Epilepsy / pathology
  • Humans
  • Mutation
  • Phenotype
  • Seizures / genetics*
  • Seizures / pathology

Substances

  • Calcium Channels
  • Drosophila Proteins
  • cac protein, Drosophila
  • Calcium