The neuromuscular junction connects the nervous system to
the muscular system via synapses between efferent nerve fibers and muscle
fibers, also known as muscle cells. As an action potential reaches the end of a
motor neuron, voltage-dependent calcium channels open allowing calcium to enter
the neuron. Calcium binds to sensor proteins (synaptotagmin) on synaptic
vesicles triggering vesicle fusion with the plasma membrane and subsequent
neurotransmitter release from the motor neuron into the synaptic cleft. In
vertebrates, motor neurons release acetylcholine (ACh), a small molecule
neurotransmitter, which diffuses through the synapse and binds nicotinic
acetylcholine receptors (nAChRs) on the plasma membrane of the muscle fiber, also
known as the sarcolemma. nAChRs are ionotropic, meaning they serve as ligand
gated ion channels. The binding of ACh to the receptor can depolarize the
muscle fiber, causing a cascade that eventually results in muscle contraction.
Structure
The neuromuscular junction is by definition a synapse, but
it differs from synapses between neurons. Presynaptic motor axons are
demyelinated and stop 30 nanometers from the sarcolemma, the cell membrane of a
muscle cell. This 30-nanometer space forms the synaptic cleft through which
signalling molecules are released. The sarcolemma has invaginations called
postjunctional folds, which increase the surface area of the membrane exposed
to the synaptic cleft. These postjunctional folds form what is referred to as
the motor endplate, which possess acetylcholine receptors (AChRs) at a density
of 10,000 receptors/micrometer 2 in skeletal muscle. The presynaptic axons form
bulges called terminal boutons that project into the postjunctional folds of
the sarcolemma. The presynaptic boutons have active zones that contain
vesicles, quanta, full of acetylcholine molecules. These vesicles can fuse with
the presynaptic membrane and release ACh molecules into the synaptic cleft via
exocytosis after depolarization. AChRs are localized opposite the presynaptic
terminals by protein scaffolds at the postjunctional folds of the sarcolemma.
Dystrophin, a structural protein, connects the sarcomere, sarcolemma, and
extracellular matrix components. Rapsyn is another protein that docks AChRs and
structural proteins to the cytoskeleton. Also present is the receptor tyrosine
kinase protein MuSK, a signaling protein involved in the development of the
neuromuscular junction, which is also held in place by rapsyn.
