PMID:15281071

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
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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

References

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