3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.4. Physiology
                  3.1.4.2. Neurophysiology
                      3.1.4.2.3. Acetylcholine
                          3.1.4.2.3.1. Acetylcholine receptors
 3.1.4.2.3.1.1. Nicotinic acetylcholine receptors 

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:

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