Neuromuscular Junction

Abstract

The neuromuscular junction (NMJ) is the site of communication between motor nerve axons and muscle fibres. It is composed of four specialised cell types: motor neurons, Schwann cells, muscle fibres and the recently discovered kranocytes. The function of the NMJ is to transmit signals from the motor neuron to the skeletal muscle fibre quickly and reliably, to ensure precise control of skeletal muscle contraction and therefore voluntary movement. The reliability of transmission is aided by specialised architecture (multiple active zones, junctional folds) that promotes high levels of transmitter release, large and reliable postsynaptic responses to transmitter binding and rapid termination of signalling events. In the last century, the structure and function of the NMJ has been extensively studied, which has been instrumental in uncovering many of the fundamental processes of chemical synaptic transmission.

Key Concepts:

  • The somatic neuromuscular junction is the site of communication between motor neurons and skeletal muscle fibres.

  • Specialisations of the neuromuscular junction mean that activity in and release of transmitter from motor neurons produces contraction of skeletal muscle fibres rapidly and reliably.

  • The neuromuscular junction comprises four cell types: the motor neuron, terminal Schwann cell, skeletal muscle fibre and kranocyte, with the motor neuron and muscle fibre separated by a gap called the synaptic cleft.

  • The motor nerve terminal contains synaptic vesicles, filled with neurotransmitter, which release their transmitter into the synaptic cleft at multiple specialised sites called active zones, in response to action potential firing.

  • Released transmitter acts at receptors on the muscle membrane, which occur in high‐density clusters at the peaks of muscle membrane infoldings called junctional folds.

  • Junctional folds are unique to the neuromuscular junction, increasing the reliability of transmission by localisation of acetylcholine receptors to the crests of the folds and enhancing the effect of depolarisation by localisation of sodium channels in the troughs.

  • Schwann cells are essential for the development and maintenance of the neuromuscular junction and play important roles in the remodelling and regeneration of damaged neuromuscular junctions.

  • Acetylcholinesterase in the synaptic cleft hydrolyses acetylcholine and limits the temporal and spatial effects of released of acetylcholine, ensuring precision of muscle control.

  • Transmitter binding causes two types of electrical signals in skeletal muscle, miniature endplate potentials caused by the spontaneous release of a single vesicle of acetylcholine and larger endplate potentials. Endplate potentials are caused by activity‐dependent release of multiple transmitter‐filled vesicles and trigger action potential firing in, and thus contraction of, the muscle fibre.

  • The neuromuscular junction is an accessible and relatively easy to study synapse that has led to tremendous progress in our understanding of synapses and in particular neurotransmitter release and continues to be a useful experimental model and educational tool.

Keywords: motor neuron; quanta; acetylcholine receptor; active zone; motor end plate; chemical synapse; synaptic transmission; transmitter release; exocyotosis

Figure 1.

Gross organisation and cell types of the somatic neuromuscular junction.

Figure 2.

Motor neurons innervating muscle fibres and forming two separate motor units.

Figure 3.

Fine structure of the somatic neuromuscular junction.

Figure 4.

Development at the mouse somatic neuromuscular junction. (a) At embryonic day 13–14, the growth cone of a motor axon approaches a site ‘prepatterned’ with acetylcholine receptors on a newly formed myotube. Schwann cell precursors follow closely behind. (b) Between embryonic days 14–16 the growth cone differentiates into a nerve terminal as an initial contact is formed on the myotube and Schwann cell precursors differentiate into immature Schwann cells. (c) At embryonic day 16, a shallow gutter forms on the surface of the myotube that will develop into junctional folds and a thin layer of basal lamina appears between the nerve terminal and myotube. (d) By birth, after 22 days in the uterus, the myotube is innervated by multiple axons from different motor neurons and terminal Schwann cells form a loose cap over groups of terminal boutons. (e) Approximately 3–4 weeks after birth, the NMJ is matured and fully functional and all but one nerve terminal are withdrawn in a process known as synapse elimination. Terminal Schwann cell processes separately cap the nerve terminal while preterminal Schwann cells form myelin.

close

References

Auld DS and Robitaille R (2003) Glial cells and neurotransmission: an inclusive view of synaptic function. Neuron 40(2): 389–400.

Balice‐Gordon RJ (1997) Age‐related changes in neuromuscular innervation. Muscle & Nerve 20(S5): 83–87.

del Castillo J and Katz B (1954) Quantal components of the end‐plate potential. Journal of Physiology 124(3): 560–573.

Court FA, Gillingwater TH, Melrose S et al. (2008) Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions. Journal of Cell Science 121(23): 3901–3911.

Engel A and Franzini‐Armstrong C (2004) Myology: Basic and Clinical. New York: McGraw‐Hill, Medical Publishing Division.

Fatt P and Katz B (1952) Spontaneous subthreshold activity at motor nerve endings. Journal of Physiology 117(1): 109–128.

Griffin JW and Thompson WJ (2008) Biology and pathology of nonmyelinating Schwann cells. Glia 56(14): 1518–1531.

Heuser JE (1977) Synaptic vesicle exocytosis revealed in quick‐frozen frog neuromuscular junctions treated with 4‐amino‐pyridine and given a single electric shock. In: Cowen WM and Ferrendelli JA (eds) Approaches to the Cell Biology of Neurons, 461 p. Washington, DC: Society for Neuroscience.

Jang YC and Van Remmen H (2010) Age‐associated alterations of neuromuscular junction. Experimental Gerontology. doi:10.1016/j.exger.2010.08.029.

Jessen KR and Mirsky R (2005) The origin and development of glial cells in peripheral nerves. Nature Reviews. Neuroscience 6(9): 671–682.

Kanning KC, Kaplan A and Henderson CE (2010) Motor neuron diversity in development and disease. Annual Review of Neuroscience 33(1): 409–440.

Richards DA, Guatimosim C, Rizzoli SO and Betz WJ (2003) Synaptic vesicle pools at the frog neuromuscular junction. Neuron 39(3): 529–541.

Rizzoli SO and Betz WJ (2004) The structural organization of the readily releasable pool of synaptic vesicles. Science 303(5666): 2037–2039.

Rizzoli SO and Betz WJ (2005) Synaptic vesicle pools. Nature Reviews. Neuroscience 6(1): 57–69.

Sanes JR and Lichtman JW (1999) Development of the vertebrate neuromuscular junction. Annual Review of Neuroscience 22(1): 389–442.

Südhof TC (2004) The synaptic vesicle cycle. Annual Review of Neuroscience 27(1): 509–547.

Unwin N (2005) Refined structure of the nicotinic acetylcholine receptor at 4 A resolution. Journal of Molecular Biology 346(4): 967–989.

Wood SJ and Slater CR (1997) The contribution of postsynaptic folds to the safety factor for neuromuscular transmission in rat fast‐ and slow‐twitch muscles. Journal of Physiology 500(part 1): 165–176.

Zhai RG and Bellen HJ (2004) The architecture of the active zone in the presynaptic nerve terminal. Physiology 19(5): 262–270.

Zucker RS and Regehr WG (2002) Short‐term synaptic plasticity. Annual Review of Physiology 64(1): 355–405.

Further Reading

Engel A (2008) Neuromuscular Junction Disorders. Edinburgh: Elsevier.

Kandel ER and Schwartz JH (2000) Principles of Neural Science. New York: McGraw‐Hill.

Kummer TT, Misgeld T and Sanes JR (2006) Assembly of the postsynaptic membrane at the neuromuscular junction: paradigm lost. Current Opinion in Neurobiology 16(1): 74–82.

Sanes JR and Lichtman JW (2001) Induction, assembly, maturation and maintenance of a postsynaptic apparatus. Nature Reviews. Neuroscience 2(11): 791–805.

Wood SJ and Slater RC (2001) Safety factor at the neuromuscular junction. Progress in Neurobiology 64(4): 393–429.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Hong, Ivan HK, and Etherington, Sarah J(Feb 2011) Neuromuscular Junction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023202]