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) Ultrafast transmission. 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. The collagen-tailed A12 acetylcholinesterase is concentrated in the synaptic cleft of NMJs and NEJs, were it curtails the postsynaptic response by ultrafast ACh hydrolysis. Here, additional processes contribute to make transmission so rapid. (2) Rapid transmission. At peripheral and central cholinergic neuro-neuronal synapses, transmission involves an initial, relatively rapid (10–50 ms) nicotinic response, followed by various muscarinic or nicotinic effects. Acetylcholinesterase (AChE) being not concentrated within these synapses, it does not curtail the initial rapid response. In contrast, the late responses are controlled by a globular form of AChE (mainly G4-AChE), which is membrane-bound and/or secreted. (3) Slow ACh signalling. In non-neuronal systems, in muscarinic domains, and in most regions of the central nervous system (CNS), many ACh-releasing structures (cells, axon terminals, varicosities, boutons) do not form true synaptic contacts, most muscarinic and also part of nicotinic receptors are extra-synaptic, often situated relatively far from ACh releasing spots. A12-AChE being virtually absent in CNS, G4-AChE is the most abundant form, whose function appears to modulate the “volume” transmission, keeping ACh concentration within limits in time and space.