Data from: 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 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.

震动敏感（Bang sensitive, BS）果蝇突变体表现出特征性的类癫痫发作表型，在某些方面与人类癫痫等发作性神经系统疾病相似。其中由电压门控钠通道（voltage-gated Na+ channel）基因功能获得性突变（gain-of-function mutation）引发的BS突变体parabss1，对癫痫发作极度敏感，其表型难以通过抗癫痫药物饲喂或癫痫发作抑制突变来缓解，已被用作人类难治性癫痫的疾病模型。本研究发现，果蝇突触前钙通道（presynaptic Ca++ channel）α1亚基基因突变cacophony（cacTS2）是一种强效的癫痫发作抑制突变，可逆转parabss1及其他BS突变体的类癫痫发作表型。与cacTS2构建双突变体组合后，parabss1的类癫痫发作表型可被抑制高达90%。令人意外的是，本研究还发现parabss1可反向抑制cacTS2的类癫痫发作表型：cacTS2突变体在暴露于高温后，会短暂表现出此类癫痫发作行为及自发性高频动作电位发放（action potential firing）；与parabss1构建双突变体组合后，cacTS2的此类癫痫发作行为可被缓解85%。