title: Synaptic vesicles: test for a role in presynaptic calcium regulation.
abstract: Membrane-bound organelles such as mitochondria and the endoplasmic reticulum play an important role in neuronal Ca(2+) homeostasis. Synaptic vesicles (SVs), the organelles responsible for exocytosis of neurotransmitters, occupy more of the volume of presynaptic nerve terminals than any other organelle and, under some conditions, can accumulate Ca(2+). They are also closely associated with voltage-gated Ca(2+) channels (VGCCs) that trigger transmitter release by admitting Ca(2+) into the nerve terminal in response to action potentials (APs). We tested the hypothesis that SVs can modulate Ca(2+) signals in the presynaptic terminal. This has been a difficult question to address because neither pharmacological nor genetic approaches to block Ca(2+) permeation of the SV membrane have been available. To investigate the possible role of SVs in Ca(2+) regulation, we used imaging techniques to compare Ca(2+) dynamics in motor nerve terminals before and after depletion of SVs. We used the temperature-sensitive Drosophila dynamin mutant shibire, in which SVs can be eliminated by stimulation. There was no difference in the amplitude or time course of Ca(2+) responses during high-frequency trains of APs, or single APs, in individual presynaptic boutons before and after depletion of SVs. SVs have a limited role, if any, in the rapid sequestration of Ca(2+) within the neuronal cytosol or the synaptic microdomain. We also conclude that SVs are not important for regulation of synaptic VGCCs.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. greg.macleod@utoronto.ca
authors.forename: Greg T
authors.initials: GT
authors.lastname: Macleod
authors.forename: Leo
authors.initials: L
authors.lastname: Marin
authors.forename: Milton P
authors.initials: MP
authors.lastname: Charlton
authors.forename: Harold L
authors.initials: HL
authors.lastname: Atwood
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D007814:Larva / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D009930:Organic Chemicals; D017729:Presynaptic Terminals / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*; D013696:Temperature
chemical_list: D005456:Fluorescent Dyes; C403124:Oregon Green BAPTA-dextran; D009930:Organic Chemicals; D002118:Calcium