The Drosophila ERG channel seizure plays a role in the neuronal homeostatic stress response.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Drosophila Proteins/*genetics ; Heat-Shock Response/*genetics ; Potassium Channels, Voltage-Gated/*genetics ; Seizures/*genetics ; Transcriptional Regulator ERG/*genetics; Animals ; Animals, Genetically Modified ; Drosophila ; Drosophila Proteins/metabolism ; Gene Knockdown Techniques ; Incidence ; Long QT Syndrome/complications ; Long QT Syndrome/genetics ; Neurons/metabolism ; Potassium Channels, Voltage-Gated/metabolism ; Reverse Genetics ; Seizures/epidemiology ; Transcriptional Regulator ERG/metabolism

Neuronal physiology is particularly sensitive to acute stressors that affect excitability, many of which can trigger seizures and epilepsies. Although intrinsic neuronal homeostasis plays an important role in maintaining overall nervous system robustness and its resistance to stressors, the specific genetic and molecular mechanisms that underlie these processes are not well understood. Here we used a reverse genetic approach in Drosophila to test the hypothesis that specific voltage-gated ion channels contribute to neuronal homeostasis, robustness, and stress resistance. We found that the activity of the voltage-gated potassium channel seizure (sei), an ortholog of the mammalian ERG channel family, is essential for protecting flies from acute heat-induced seizures. Although sei is broadly expressed in the nervous system, our data indicate that its impact on the organismal robustness to acute environmental stress is primarily mediated via its action in excitatory neurons, the octopaminergic system, as well as neuropile ensheathing and perineurial glia. Furthermore, our studies suggest that human mutations in the human ERG channel (hERG), which have been primarily implicated in the cardiac Long QT Syndrome (LQTS), may also contribute to the high incidence of seizures in LQTS patients via a cardiovascular-independent neurogenic pathway.
Competing Interests: The authors have declared that no competing interests exist.

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P40 OD010949 United States OD NIH HHS; P40 OD018537 United States OD NIH HHS; R01 GM084947 United States GM NIGMS NIH HHS; R21 NS089834 United States NS NINDS NIH HHS

0 (Drosophila Proteins)
0 (ERG protein, human)
0 (Potassium Channels, Voltage-Gated)
0 (Transcriptional Regulator ERG)
0 (sei protein, Drosophila)

Date Created: 20190809 Date Completed: 20200107 Latest Revision: 20240922

20250114

PMC6687100

10.1371/journal.pgen.1008288

31393878