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- Title
Exocytosis, Mediatophore, and Vesicular Ca<sup>2+</sup>/H<sup>+</sup> Antiport in Rapid Neurotransmission.
- Authors
Dunant, Yves; Cordeiro, J. Miguel; Gonçalves, Paula P.
- Abstract
In rapid synapses, neurotransmitter quanta are emitted in less than 100 μs, often at a high frequency. Using fast cryofixation of synapses, we found a very brief (2–3 ms) change affecting intramembrane particles in presynaptic membrane. Vesicle openings also occurred but after a significant delay. The particle change is most probably linked to mediatophore, a proteolipid of 220 kDa. Mediatophore aggregates were demonstrated in active zones of the presynaptic membrane. Reconstituted in liposomes, Xenopus oocytes, and neuroblastoma cells, mediatophore releases acetylcholine in a Ca2+-dependent and quantal manner, mimicking physiological release. In restricted presynaptic “nanodomains,” Ca2+ concentration explosively reaches a high level and then vanishes with a time constant of 300–400 μs. Among the processes contributing to the fast phase of Ca2+ buffering, a vesicular Ca2+/H+ antiport plays a major role. Energized by the Vesicular-ATPase-dependent proton gradient, the antiport has a low affinity for Ca2+. We inactivated the Ca2+/H+ antiport using bafilomycin A1, which annihilates the proton gradient. As a result, the postsynaptic potential was increased in duration for about 3 ms, an effect caused by persistence of transmitter release. A similar change was obtained by replacing extracellular Ca2+ by strontium, which inhibits the antiport. The antiport function, therefore, is to abbreviate the presynaptic Ca2+ signal, making transmitter release briefer. This allows transmission to operate at high frequency. Following a brief period of stimulation, calcium transiently accumulates in synaptic vesicles where it is exchanged against transmitter. Calcium is subsequently cleared from the terminal, most probably by exocytosis.
- Subjects
EXOCYTOSIS; NEURAL transmission; NEUROTRANSMITTERS; SYNAPSES; COATED vesicles; PROTEINS; CELL physiology; CYTOLOGY; BIOLOGY
- Publication
Annals of the New York Academy of Sciences, 2009, Vol 1152, p100
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.2008.04000.x