Genetic Suppression of Seizure Susceptibility in Drosophila

• Published in: Journal of neurophysiology 2001-09, Vol.86 (3), p.1211-1225
• Main Authors: Kuebler, Daniel, Zhang, Haiguang, Ren, Xiaoyun, Tanouye, Mark A
• Format: Article
• Language: English
• Subjects: Animals; Chromosomal Proteins, Non-Histone; Connexins - genetics; DNA Helicases; DNA-Binding Proteins; Drosophila; Drosophila - genetics; Drosophila Proteins; Electrophysiology; Epilepsy - genetics; Epilepsy - physiopathology; Ether-A-Go-Go Potassium Channels; Female; Genetic Predisposition to Disease; Genotype; Large-Conductance Calcium-Activated Potassium Channels; Male; Mutation - physiology; Nerve Tissue Proteins - genetics; Neural Pathways - physiology; Phenotype; Potassium Channels - genetics; Potassium Channels, Calcium-Activated; RNA Helicases - genetics; Shaker Superfamily of Potassium Channels; Sodium Channels - genetics; Suppression, Genetic; Transcription Factors - genetics
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.2001.86.3.1211

  1 Department of Environmental Science, Policy and Management, Division of Insect Biology and   2 Department of Molecular and Cell Biology, Division of Neurobiology, University of California, Berkeley, California 94720 Kuebler, Daniel, Haiguang Zhang, Xiaoyun Ren, and Mark A. Tanouye. Genetic Suppression of Seizure Susceptibility in Drosophila . J. Neurophysiol. 86: 1211-1225, 2001. Despite the frequency of seizure disorders in the human population, the genetic and physiological basis for these defects has been difficult to resolve. Although many genetic defects that cause seizure susceptibility have been identified, the defects involve disparate biological processes, many of which are not neural specific. The large number and heterogeneous nature of the genes involved makes it difficult to understand the complex factors underlying the etiology of seizure disorders. Examining the effect known genetic mutations have on seizure susceptibility is one approach that may prove fruitful. This approach may be helpful both in understanding how different physiological processes affect seizure susceptibility and in identifying novel therapeutic treatments. In this study, we have taken advantage of Drosophila , a genetically tractable system, to identify factors that suppress seizure susceptibility. Of particular interest has been a group of Drosophila mutants, the bang-sensitive (BS) mutants, which are much more susceptible to seizures than wild type. The BS phenotypic class includes at least eight genes, including three examined in this study, bss, eas, and sda. Through the generation of double-mutant combinations with other well-characterized Drosophila mutants, the BS mutants are particularly useful for identifying genetic factors that suppress susceptibility to seizures. We have found that mutants affecting Na + channels, mle napts and para , K + channels, Sh , and electrical synapses, shak-B 2 , can suppress seizures in the BS mutants. This is the first demonstration that these types of mutations can suppress the development of seizures in any organism. Reduced neuronal excitability may contribute to seizure suppression. The best suppressor, mle napts , causes an increased stimulation threshold for the giant fiber (GF) consistent with a reduction in single neuron excitability that could underlie suppression of seizures. For some other double mutants with para and Sh KS133 , there are no GF threshold changes, but reduced excitability may also be indicated by a r