Physiology: Synaptic Transmission

Physiology: Synaptic Transmission

Conduction Along Myelinated vs Unmyelinated Axons

In unmyelinated fibres, depolarisation spreads continuously along the entire axon membrane — slow, high-energy. In myelinated fibres, myelin (produced by Schwann cells in PNS, oligodendrocytes in CNS) covers internodal segments. Myelin increases membrane resistance (rm) and decreases membrane capacitance — depolarisation jumps from one node of Ranvier to the next (saltatory conduction). This is approximately 50× faster and more energy-efficient than continuous conduction.

Demyelination disrupts saltatory conduction; effects include: conduction slowing, conduction block at high frequencies, and ectopic impulse generation (abnormal spontaneous firing between nodes). Multiple sclerosis is the classic CNS demyelinating disease; Guillain-Barré syndrome affects PNS myelin.

Chemical Synaptic Transmission — Eight Steps

1. AP arrives at presynaptic axon terminal (bouton).
2. Depolarisation opens voltage-gated Ca²⁺ channels in the presynaptic membrane.
3. Ca²⁺ enters the bouton down its electrochemical gradient.
4. Ca²⁺ triggers SNARE protein complex assembly (synaptobrevin on vesicle + syntaxin + SNAP-25 on membrane), causing vesicle fusion with the presynaptic membrane (exocytosis).
5. Neurotransmitter (NT) is released into the synaptic cleft.
6. NT diffuses across the cleft and binds to postsynaptic receptors.
7. Receptor activation causes ion flow → EPSP (excitatory) or IPSP (inhibitory).
8. NT is removed: enzymatic breakdown (e.g., AChE degrades ACh), re-uptake into presynaptic terminal (e.g., monoamines), diffusion away, or glial uptake (e.g., glutamate by astrocytes).

Receptor Types

Ionotropic receptors (ligand-gated ion channels): NT binding directly opens an ion channel → fast (milliseconds) postsynaptic effect. Examples: nAChR (Na⁺/K⁺), GABA-A (Cl⁻), AMPA/NMDA (glutamate, Na⁺/K⁺ ± Ca²⁺). Metabotropic receptors (G protein-coupled): NT binding activates a G protein → second-messenger cascade (e.g., cAMP, IP₃/DAG) → slower, more prolonged effects. Examples: muscarinic ACh receptors, GABA-B, metabotropic glutamate receptors.

Presynaptic Modulation

Ca²⁺ entry is essential for NT release. Botulinum toxin cleaves SNARE proteins → prevents vesicle fusion → flaccid paralysis. α-Latrotoxin (black widow spider venom) causes massive NT release. Botulinum toxin is used therapeutically to treat focal dystonia, spasticity, and hyperhidrosis.