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Genetic Modifications of Seizure Susceptibility and Expression by Altered Excitability in Drosophila Na⁺ and K⁺ Channel Mutants

Department of Biological Sciences, University of Iowa, Iowa City, Iowa

Submitted 10 May 2006; accepted in final form 6 June 2006

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 nap^ts flies 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 Sh¹³³ and Hk mutants promoted ID induction. However, only Sh¹³³ but 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 nap^ts in bss nap double mutants, whereas Sh heightened seizure susceptibility in bss Sh¹³³ and bss Sh^M double 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.

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				I-F. Peng and C.-F. Wu Differential Contributions of Shaker and Shab K+ Currents to Neuronal Firing Patterns in Drosophila J Neurophysiol, January 1, 2007; 97(1): 780 - 794. [Abstract] [Full Text] [PDF]