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PMID:15281071

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Citation

Trotta, N, Rodesch, CK, Fergestad, T and Broadie, K (2004) Cellular bases of activity-dependent paralysis in Drosophila stress-sensitive mutants. J. Neurobiol. 60:328-47

Abstract

Stress-sensitive mutants in Drosophila have been shown to exhibit activity-dependent defects in neurotransmission. Using the neuromuscular junction (NMJ), this study investigates synaptic function more specifically in two stress-sensitive mutants: stress-sensitive B (sesB), which encodes a mitochondrial ADP/ATP translocase (ANT); and Atpalpha(2206), a conditional mutant of the Na+/K+ ATPase alpha-subunit. Mechanical shock induces a period of brief paralysis in both homozygous and double heterozygous mutants, but further analysis revealed distinct activity-dependent neurotransmission lesions in each mutant. Basal neurotransmission appeared similar to wild-type controls in both mutants under low frequency stimulation. High frequency stimulation, however, caused pronounced synaptic fatigue as well as slow and incomplete synaptic recovery in sesB mutants while Atpalpha(2206) mutants displayed an increase (25-fold) in synaptic failures. Perhaps to compensate for these activity dependent defects, the neuromuscular synapse was found to be overgrown in both mutants. Passive electrotonic stimulation, which initiates synaptic transmission independent of action potentials, ameliorated synaptic failures and resulted in increased neurotransmission amplitude in Atpalpha(2206) mutants. In addition, spontaneous synaptic vesicle fusion rates were increased in Atpalpha(2206) mutants, suggesting that, in the absence of action potential requirements, these synaptic terminals are healthy, if not hyperactive. Dye labeling studies revealed aberrant synaptic vesicle cycling in sesB mutants indicating a reduction of functional synaptic vesicles. We therefore postulate that both stress-sensitive mutants harbor unique neurotransmission defects: Atpalpha(2206) mutants are unable to maintain ionic gradients required during repetitive action potential propagation, and sesB mutants cannot maintain synaptic vesicle cycling during periods of high demand.

Links

PubMed Online version:10.1002/neu.20017

Keywords

Animals; Behavior, Animal; Calcium/metabolism; Drosophila/physiology; Electrophysiology/methods; Evoked Potentials/genetics; Evoked Potentials/radiation effects; Excitatory Postsynaptic Potentials/genetics; Excitatory Postsynaptic Potentials/radiation effects; Genes, Insect; Hot Temperature; Larva/physiology; Mitochondria/metabolism; Mutation; Neuromuscular Junction/genetics; Neuromuscular Junction/physiopathology; Paralysis/physiopathology; Physical Stimulation; Presynaptic Terminals; Pyridinium Compounds/metabolism; Quaternary Ammonium Compounds/metabolism; Stress, Physiological/genetics; Stress, Physiological/physiopathology; Synaptic Transmission/genetics; Synaptic Transmission/radiation effects; Synaptic Vesicles/metabolism; Time Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:ATNA

involved_in

GO:0051124: synaptic assembly at neuromuscular junction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ADT

involved_in

GO:0048489: synaptic vesicle transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ADT

involved_in

GO:0007268: chemical synaptic transmission

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ADT

involved_in

GO:0001508: action potential

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ADT

involved_in

GO:0051124: synaptic assembly at neuromuscular junction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ATNA

involved_in

GO:0007268: chemical synaptic transmission

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ATNA

involved_in

GO:0051124: synaptic growth at neuromuscular junction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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