Prejunctional Effects
Prejunctional receptors are involved in the modulation of acetylcholine
release in the neuromuscular junction. The existence of both nicotinic and muscarinic
receptors on motor nerve endings has been described. The prejunctional nicotinic
receptor is a pentameric complex composed of α3
β2
-subunits.
Bowman[32]
suggested that the prejunctional nicotinic
receptors are activated by acetylcholine and function in a positive-feedback control
system that serves to maintain the availability of acetylcholine when demand for
it is high (e.g., during tetany).[32]
Blockage
of these receptors by nondepolarizing neuromuscular blockers would explain the fade
phenomenon seen with tetanic and train-of-four (TOF) stimulation.[32]
[33]
The G protein-coupled muscarinic receptors
are also involved in the feedback modulation of acetylcholine release.[34]
[35]
[36]
The prejunctional
M1
and M2
receptors are involved in facilitation and inhibition
of acetylcholine release, respectively, through modulation of Ca2+
influx,
[37]
[38]
whereas
the prejunctional nicotinic receptors are involved in mobilization of acetylcholine,
but not in the release process directly.[39]
Hence,
blockade of prejunctional nicotinic receptors by nondepolarizing neuromuscular blockers
prevents acetylcholine from being made available fast enough to support tetanic or
TOF stimulation. In contrast, prejunctional muscarinic receptors are involved in
upmodulation or downmodulation of the release mechanism. No evidence has indicated
that nondepolarizing neuromuscular blockers act on muscarinic receptors.
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