The pre- and postsynaptic elements are separated by a 20 to 30 nm wide cleft called the synaptic cleft. The synaptic cleft contains enzymes that destroy the neurotransmitters released into the cleft. Synaptic transmission occurs through the following steps:
(1) The action potential arriving at the presynaptic nerve terminal depolarizes the presynaptic nerve terminal.
(2) The depolarization stimulates the influx of free Ca2+ into the nerve terminal by opening of voltage-gated Ca2+ channels.
(3) Ca2+ stimulates the sliding of synaptic vesicles along the presynaptic grid towards the presynaptic membrane, presumably by triggering the cross-bridge movements.
(4) The vesicles discharge their neurotransmitters into the synaptic cleft by exocytosis.
(5) The neurotransmitter released from the presynaptic terminal do not persist in the synaptic cleft for long as it is removed from these in one of the following ways:
(i) reuptake by the presynaptic terminal, which by far is the commonest mechanism. Exceptions are peptide neurotransmitter and acetylcholine;
(ii) rapid dissociation by enzymatic action e.g. acetylcholine is dissociated by acetyl-cholinesterase into acetyl CoA and choline and only the choline is taken up; and
(iii) diffusion away from the synaptic cleft.