PMID:16272407

Citation	Fergestad, T, Ganetzky, B and Palladino, MJ (2006) Neuropathology in Drosophila membrane excitability mutants. Genetics 172:1031-42
Abstract	Mutations affecting ion channels and neuronal membrane excitability have been identified in Drosophila as well as in other organisms and characterized for their acute effects on behavior and neuronal function. However, the long-term effect of these perturbations on the maintenance of neuronal viability has not been studied in detail. Here we perform an initial survey of mutations affecting Na+ channels and K+ channels in Drosophila to investigate their effects on life span and neuronal viability as a function of age. We find that mutations that decrease membrane excitability as well as those that increase excitability can trigger neurodegeneration to varying degrees. Results of double-mutant interactions with dominant Na+/K+ ATPase mutations, which themselves cause severe neurodegeneration, suggest that excitotoxicity owing to hyperexcitability is insufficient to explain the resultant phenotype. Although the exact mechanisms remain unclear, our results suggest that there is an important link between maintenance of proper neuronal signaling and maintenance of long-term neuronal viability. Disruption of these signaling mechanisms in any of a variety of ways increases the incidence of neurodegeneration.
Links	PubMed PMC1456203 Online version:10.1534/genetics.105.050625
Keywords	Age Factors; Animals; Brain/pathology; Cell Membrane/pathology; Drosophila Proteins/genetics; Drosophila melanogaster/genetics; Drosophila melanogaster/physiology; Longevity/genetics; Membrane Potentials/genetics; Neurons/pathology; Neurons/physiology; Potassium Channels/genetics; Sodium Channels/genetics; Sodium-Potassium-Exchanging ATPase/genetics
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