Until 1950-1960, most physiologists were reluctant to accept chemical neurotransmission. They believed that chemical reactions were much too slow to account for the speed of synaptic processes. The first breakthrough was to discover the impressive velocity of acetylcholinesterase. Then, nicotinic receptors provided an example of complex ultrarapid reactions: fast activation at a low ligand affinity, then desensitization if the ligand is not rapidly removed. Here, we describe synaptic transmission as a chain of low-affinity rapid reactions, assisted by many slower regulatory processes. For starting quantal acetylcholine release, mediatophores are activated by high Ca2+ concentrations, but they desensitize at a higher affinity if Ca2+ remains present. Several mechanisms concur to the rapid removal of Ca2+ from the submembrane microdomains. Among them, the Ca2+/H+ antiport is a typical low-affinity, high-speed process that certainly contributes to the rapidity of neurotransmission.