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doi:10.1534/genetics.105.050625
A more recent version of this article appeared on February 1, 2006.
REGULAR RESEARCH PAPERS |
Neuropathology in Drosophila Membrane Excitability Mutants
Tim Fergestad 1, Barry Ganetzky 1 and Michael J. Palladino 2*
1 University of Wisconsin
2 University of Pittsburgh School of Medicine
* To whom correspondence should be addressed. E-mail: mjp44{at}pitt.edu.
Submitted on September 6, 2005
Revised on October 3, 2005
Accepted on 24 October 2005
Mutations affecting ion channels and neuronal membrane excitability have been identified in Drosophila as well as 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 lifespan 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.
Key Words: Channelopathies, Hyperexcitability, Ion channel, Neurodegeneration, Sodium pump
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