Nicotinic acetylcholine receptors (nAChR)

[WG21:p101-103]

• Subdivided into two groups, depending on the locations
  * Neuromuscular junctions
  * Autonomic ganglia and CNS
  * Adrenal medullar [???]
• Nicotinic ACh receptors are members of ligand-gated ion channels
  * GABAa and glycine receptors are also ligand-gated ion channels
• Made up of 5 subunits
  * 2 alpha units, beta, gamma, and epsilon
  * ACh binds to each alpha subunit
  * Delta and epsilon subunits stabilise the closed state of nAChR
• When both alpha subunits are bound
  --> Configurational change
  --> Channel opens
  --> Increased conductance of Na+ and other cations (including Ca2+)

NB:

• Many of the nACh receptors in brain are located presynaptically on glutamine-secreting axon terminals

Foetal nAChR

• Delta subunit (instead of epsilon) is found in foetal nAChRs
• Longer period of opening than the adult type
• Lower conductance to Na+, K+, Ca2+ than the adult type
• A single ACh quanta can elicit action potential [SH4:p214]
• At birth, there is a mixture of nACh receptors with epsilon and those with delta subunits
• Majority of extrajunctional receptors are of foetal type

NB:

• See Neuromuscular junction for prejunctional nAChR and extrajunctional nAChRs

Regulation of the nAChRs

Up-regulation of nAChRs

• Spinal cord injury
• Cerebral vascular accident
• Thermal injury
• Prolonged immobility
• Prolonged exposure to NMBDs
• Multiple sclerosis
• Guillain-Barre syndrome

Down-regulation of nAChRs

• Myasthenia gravis
• Anticholinesterase overdose
• Organophosphate poisoning