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Presynaptic K+ Channels, Vesicular Ca2+/H+ Antiport—Synaptotagmin, and Acetylcholinesterase, Three Mechanisms Cutting Short the Cholinergic Signal at Neuromuscular and Nerve-Electroplaque Junctions

Dunant, Yves ; Cordeiro, J.

In: Journal of Molecular Neuroscience, 2014, vol. 53, no. 3, p. 377-386

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    Titre
    • Presynaptic K+ Channels, Vesicular Ca2+/H+ Antiport—Synaptotagmin, and Acetylcholinesterase, Three Mechanisms Cutting Short the Cholinergic Signal at Neuromuscular and Nerve-Electroplaque Junctions
    Auteur
    • Dunant, Yves. Neurosciences fondamentales, Faculté de Médecine, Université de Genève, 1211, Genève 4, Switzerland
    • Cordeiro, J.. Lab. Farmacologia e Neurobiologia, UMIB-ICBAS, Universidade do Porto, 4050-313, Porto, Portugal
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Journal of Molecular Neuroscience, 2014, vol. 53, no. 3, p. 377-386. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:326215
    Summary
    In neuromuscular and nerve-electroplaque junctions, nerve impulses can be transmitted at high frequencies. This implies that transmission of individual impulses must be very brief. We describe three mechanisms which curtail the time course of individual impulses at these synapses: (1) opening of presynaptic K+ channels (delayed rectifier) efficiently curtails the presynaptic action potential. Inhibition of K+ channel by aminopyridines transforms the normally brief postsynaptic potential (2-3ms) to a long-lasting "giant” potential (exceeding half a second); (2) a low-affinity Ca2+/H+ antiport ensures rapid Ca2+ sequestration into synaptic vesicles, curtailing the calcium signal and thereby the duration of transmitter release. Indeed vesicular Ca2+/H+ antiport inhibition by bafilomycin or Sr2+ prolongs the duration of the postsynaptic potential. We recently showed that synaptotagmin-1 is required for this antiport activity; thus the vesicular Ca2+/H+ antiport might be synaptotagmin itself, or regulated by it; and (3) it is recalled that, in these junctions, acetylcholinesterase is highly concentrated in the synaptic cleft and that anticholinesterases lengthen the endplate time course. Therefore, at three different steps of synaptic transmission, an efficient mechanism curtails the local synaptic signal. When one of these three mechanisms is inhibited, the duration of individual impulses is prolonged, but the synapse loses its faculty to fire at high frequencies.