Exocytosis, mediatophore, and vesicular Ca2+/H+ antiport in rapid neurotransmission.

Abstract

In rapid synapses, neurotransmitter quanta are emitted in less than 100 mus, 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 Ca(2+)-dependent and quantal manner, mimicking physiological release. In restricted presynaptic "nanodomains," Ca(2+) concentration explosively reaches a high level and then vanishes with a time constant of 300-400 micros. Among the processes contributing to the fast phase of Ca(2+) buffering, a vesicular Ca(2+)/H(+) antiport plays a major role. Energized by the Vesicular-ATPase-dependent proton gradient, the antiport has a low affinity for Ca(2+). We inactivated the Ca(2+)/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 Ca(2+) by strontium, which inhibits the antiport. The antiport function, therefore, is to abbreviate the presynaptic Ca(2+) 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.

• Authors: Yves Dunant, J Miguel Cordeiro, Paula P Gonçalves
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1152 Pg. 100-12 (Jan 2009) ISSN: 1749-6632 [Electronic] United States
• PMID: 19161381 (Publication Type: Journal Article)

Chemical References

• Antiporters
• Cation Transport Proteins
• Nerve Tissue Proteins
• Receptors, Cholinergic
• calcium-hydrogen antiporters
• mediatophore
• Calcium

Topics

• Animals
• Antiporters (metabolism)
• Calcium (metabolism)
• Cation Transport Proteins (metabolism)
• Exocytosis
• Nerve Tissue Proteins (metabolism)
• Receptors, Cholinergic (metabolism)
• Synaptic Transmission