Ultrafast and Slow Cholinergic Transmission. Different Involvement of Acetylcholinesterase Molecular Forms.

Acetylcholine (ACh), an ubiquitous mediator substance broadly expressed in nature, acts as neurotransmitter in cholinergic synapses, generating specific communications with different time-courses. (1) . Vertebrate neuromuscular junctions (NMJs) and nerve-electroplaque junctions (NEJs) are the fastest cholinergic synapses; able to transmit brief impulses (1-4 ms) at high frequencies.

Presynaptic K(+) channels, vesicular Ca(2+)/H (+) antiport--synaptotagmin, and acetylcholinesterase, three mechanisms cutting short the cholinergic signal at neuromuscular and nerve-electroplaque junctions.

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.

Synaptotagmin 1 is required for vesicular Ca²⁺/H⁺-antiport activity.

A low-affinity Ca²⁺/H⁺-antiport was described in the membrane of mammalian brain synaptic vesicles. Electrophysiological studies showed that this antiport contributes to the extreme brevity of excitation-release coupling in rapid synapses. Synaptotagmin-1, a vesicular protein interacting with membranes upon low-affinity Ca²⁺-binding, plays a major role in excitation-release coupling, by synchronizing calcium entry with fast neurotransmitter release.

Synaptic vesicles control the time course of neurotransmitter secretion via a Ca²+/H+ antiport.

We investigated the physiological role of the vesicular Ca2+/H+ antiport in rapid synaptic transmission using the Torpedo electric organ (a modified neuromuscular system). By inhibiting V-type H+-transporting ATPase (V-ATPase), bafilomycin A1 dissipates the H+ gradient of synaptic vesicles, thereby abolishing the Ca2+/H+ antiport driving force. In electrophysiology experiments, bafilomycin A1 significantly prolonged the duration of the evoked electroplaque potential.

Ultra-fast versus sustained cholinergic transmission: a variety of different mechanisms.

Although synaptic transmission was assumed to use the same mechanisms in the case of different synapses of the central and peripheral nervous system, recent research revealed a great variety of different processes. Time might be a crucial factor to be considered in this diversity. It is recalled that the speed of a chemical reaction is inversely related to affinity.