Abstract
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 (2–3 ms) 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.
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Abbreviations
- ACh:
-
Acetylcholine
- AChE:
-
Acetylcholinesterase
- AP:
-
Action potential
- AmPy:
-
Aminopyridine
- EPP:
-
Endplate potential or electroplaque potential
- MEPPs:
-
Miniature endplate or miniature electroplaque potentials
- NEJ:
-
Nerve–electroplaque junction
- NMJ:
-
Neuromuscular junction
- V-ATPase:
-
Vacuolar H+-transporting adenosine triphosphatase
- VOCCs:
-
Voltage-operated calcium channels
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Dunant, Y., Cordeiro, J.M. Presynaptic K+ Channels, Vesicular Ca2+/H+ Antiport—Synaptotagmin, and Acetylcholinesterase, Three Mechanisms Cutting Short the Cholinergic Signal at Neuromuscular and Nerve–Electroplaque Junctions. J Mol Neurosci 53, 377–386 (2014). https://doi.org/10.1007/s12031-013-0212-4
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DOI: https://doi.org/10.1007/s12031-013-0212-4