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).