Go
to the main content page
The
neuromuscular junction. Acetylcholine receptors
Acetylcholine
receptors are ion channels that span the postsynaptic membrane,
and they have extracellular, intramembranous, and cytoplasmic
portions. They are located principally over thepeaks of
the postsynaptic folds, where they are present at high density.
They consist of five subunits arranged around the central
ion channel. One of the subunits is represented twice. The
different subunits are products of separate genes. This
implies that the acetylcholine receptor has been highly
conserved in evolution and suggests that the genes coding
for the different subunits may have evolved from a single
primeval acetylcholine receptor gene.
Models
of acetylcholine receptors indicate that its structure contains
an extracellular N-terminal portion, several intramembranous
portions (of which one provides part of the wall of the
ion channel) separated by short intracellular and extracellular
portions, and a cytoplasmic C-terminal part.
The
supply of junctional acetylcholine receptors is continuously
renewed. Receptors are internalized by the muscle cell and
degraded in lysosomes (specialized cytoplasmic organelles),
while new receptors are synthesized and inserted into the
muscle membrane.
In
normally innervated muscle, receptors are confined to the
neuromuscular junction. In non-innervated fetal muscle and
in denervated adult muscle, however, acetylcholine receptors
are found elsewhere as well. These receptors have slightly
different properties from junctional receptors, notably
a much higher rate of turnover.
Acetylcholine/acetylcholine
receptor interaction
The resting membrane potential of the muscle cell is held
at about -80 millivolt. Binding of acetylcholine to each
of the two alpha subunits causes the receptor molecule to
alter its configuration so that the ion channel is opened
for about one millisecond (0.001 second). This permits the
entry of small positive ions, mainly sodium. The resulting
local depolarization (the end plate potential) causes voltage-gated
sodium channels located around the end plate to open. At
a critical point (the firing threshold for the muscle cell)
a self-generating action potential is triggered, causing
the membrane potential to reverse and become briefly positive.
The action potential propagates over the muscle fibre membrane
to activate the contractile process.
The
amplitude of the end plate potential is normally sufficient
to bring the membrane potential of the muscle cell well
above the critical firing threshold. The extent to which
it does so represents a “safety factor” for neuromuscular
transmission. The safety factor will be reduced by any event
that, by interfering with presynaptic or postsynaptic function,
reduces the size of the end plate potential.
John
M. Newsom-Davis