Basic principles of neuromuscular transmission.
Neuromuscular transmission at the skeletal muscle occurs when a quantum of acetylcholine from the nerve ending is released and binds to the nicotinic acetylcholine receptors on the postjunctional muscle membrane. The nicotinic acetylcholine receptors on the endplate respond by opening channels for the influx of sodium ions and subsequent endplate depolarisation leads to muscle contraction. The acetylcholine immediately detaches from the receptor and is hydrolysed by acetylcholinesterase enzyme. Suxamethonium is a cholinergic agonist stimulating the muscle nicotinic acetylcholine receptors prior to causing neuromuscular block. Non-depolarising neuromuscular blocking drugs bind to the nicotinic acetylcholine receptors preventing the binding of acetylcholine. Non-depolarising neuromuscular blocking drugs also inhibit prejunctional alpha3beta2 nicotinic acetylcholine autoreceptors, which can be seen in the clinical setting as train-of-four fade. In some pathological states such as denervation, burns, immobilisation, inflammation and sepsis, there is expression of other subtypes of nicotinic acetylcholine receptors with upregulation of these receptors throughout the muscle membrane. The responses of these receptors to suxamethonium and non-depolarising neuromuscular blocking drugs are different and explain some of the aberrant responses to neuromuscular blocking drugs.
Martyn
J A J
JA
Harvard Medical School, Director Clinical & Biological Pharmacology Laboratory, Department of Anesthesiology, Massachusetts General Hospital, Boston, MA, USA. jmartyn@etherdome.mgh.harvard.edu
Fagerlund
M Jonsson
MJ
Eriksson
L I
LI
D006801:Humans; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology
D009466:Neuromuscular Blocking Agents; D011950:Receptors, Cholinergic