Expansion
Depolarisation, calcium entry, vesicle fusion, receptor binding, then termination
Expansion
- Action potential reaches the presynaptic terminal
- Voltage-gated calcium channels open; calcium enters
- Calcium triggers vesicle fusion with the membrane via SNARE proteins
- Neurotransmitter is released into the cleft by exocytosis
- Binds postsynaptic receptors, producing an excitatory or inhibitory postsynaptic potential
- Termination by reuptake, enzymatic degradation or diffusion
Every step is a drug or toxin target:
- Calcium entry: magnesium blocks it (hence its use in eclampsia and its muscle weakness), and Lambert-Eaton syndrome involves antibodies against these channels
- Vesicle fusion: botulinum toxin cleaves SNARE proteins, preventing release; tetanus toxin does the same at inhibitory synapses
- Receptor: myasthenia gravis, curare, and most psychotropic drugs
- Termination: SSRIs block reuptake; anticholinesterases block degradation
Postsynaptic potentials are graded and summate both spatially and temporally, in contrast to the all-or-none action potential.