Genetic Modifications of Seizure Susceptibility and Expression by Altered Excitability inDrosophilaNa+and K+Channel Mutants

Abstract

A seizure-paralysis repertoire characteristic of Drosophila “bang-sensitive” mutants can be evoked electroconvulsively in tethered flies, in which behavioral episodes are associated with synchronized spike discharges in different body parts. Flight muscle DLMs (dorsal longitudinal muscles) display a stereotypic sequence of initial and delayed bouts of discharges (ID and DD), interposed with giant fiber (GF) pathway failure and followed by a refractory period. We examined how seizure susceptibility and discharge patterns are modified in various K+and Na+channel mutants. Decreased numbers of Na+channels in naptsflies drastically reduced susceptibility to seizure induction, eliminated ID, and depressed DD spike generation. Mutations of different K+channels led to differential modifications of the various components in the repertoire. Altered transient K+currents in Sh133and Hk mutants promoted ID induction. However, only Sh133but not Hk mutations increased DD seizure and GF pathway failure durations. Surprisingly, modifications in sustained K+currents in eag and Shab mutants increased thresholds for DD induction and GF pathway failure. Nevertheless, both eag and Shab, like Sh133, increased DD spike generation and recovery time from GF pathway failure. Interactions between channel mutations with the bang-sensitive mutation bss demonstrated the role of membrane excitability in stress-induced seizure-paralysis behavior. Seizure induction and discharges were suppressed by naptsin bss nap double mutants, whereas Sh heightened seizure susceptibility in bss Sh133and bss ShMdouble mutants. Our results suggest that individual seizure repertoire components reflect different neural network activities that could be differentially altered by mutations of specific ion channel subunits.