Seizure suppression by shakB2, a gap junction mutation in Drosophila

Seizure suppression by shakB(2), a gap junction mutation in Drosophila. J Neurophysiol 95: 627-635, 2006. First published September 28, 2005; doi: 10.1152/jn. 01059.2004. Gap junction proteins mediate electrical synaptic transmission. In Drosophila, flies carrying null mutations in the shakB locus, such as shakB(2), have behavioral and electrophysiological defects in the giant fiber (GF) system neurocircuit consistent with a loss of transmission at electrical synapses. The shakB(2) mutation also affects seizure susceptibility. Mutant flies are especially seizure-resistant and have a high threshold to evoked seizures. In addition, in some double mutant combinations with epilepsy mutations, shakB(2) appears to act as a seizure-suppressor mutation: shakB(2) restores seizure susceptibility to the wild-type range in the double mutant. In double mutant combinations, shakB(2) completely suppresses seizures caused by slamdance (sda), knockdown (kdn), and jitterbug (jbug) mutations. Seizures caused by easily shocked (eas) and technical knockout (tko) mutations are partially suppressed by shakB(2). Seizures caused by bang-sensitive (bas(2)) and bang-senseless (bss(1), bss(2) alleles) mutations are not suppressed by shakB(2). These results show the use of Drosophila as a model system for studying the kinds of genetic interactions responsible for seizure susceptibility, bringing us closer to unraveling the complexity of seizure disorders in humans.