An action potential arriving at the presynaptic terminal opens voltage-gated Ca²⁺ channels. Calcium influx triggers SNARE proteins (synaptobrevin, syntaxin, SNAP-25) to fuse vesicles with the membrane, releasing neurotransmitter into the cleft.
Neurotransmitter diffuses across the ~20 nm synaptic cleft in microseconds and binds ionotropic or metabotropic receptors. Binding follows mass-action kinetics: rate depends on NT concentration and receptor occupancy.
Signal termination occurs via reuptake transporters (SERT, DAT, NET), enzymatic degradation (acetylcholinesterase cleaves ACh), or diffusion. SSRIs block serotonin reuptake, prolonging receptor activation.
Del Castillo & Katz (1954) showed synaptic transmission is quantized: each vesicle contains ~5000 NT molecules. The end-plate potential amplitude is a Poisson-distributed multiple of the single-quantal response.