Sensitivity to seizure-like activity in Drosophila following acute hypoxia and hypercapnia

Human seizure disorders represent a heterogeneous collection of neuropathies, many of which are poorly understood. To investigate the etiology of seizure disorders, we have used a group of Drosophila mutants known as the bang-sensitive (BS) paralytics. The BS mutants exhibit seizure-like activity (SLA) following a wide variety of insults including mechanical shock, electrical shock, high frequency light and cold temperatures. In this study, we show that two novel insults, hypoxia and hypercapnia (elevated CO(2) levels) are potent triggers of SLA in a number of the BS mutants. We also show that both of these insults, hypoxia and hypercapnia, can trigger SLA in wild-type flies as well. However, we find that the BS mutants are more susceptible than wild-type flies to these insults as they exhibit more SLA following these insults and, in the case of hypercapnia, they exhibit SLA at a lower threshold. In addition, we demonstrate that the BS mutants are more susceptible to the anesthetizing effects of CO(2) as compared to wild-type flies. The increased sensitivity to both hypoxia and hypercapnia in these BS mutants suggests possible physiological defects that may underlie seizure susceptibility.