Nicotinic Acetylcholine Receptors in Muscle

Abstract

Acetylcholine is the neurotransmitter carrying the excitatory signal at the neuromuscular endplate from the presynaptic to the postsynaptic side across the synaptic cleft. Together with acetylcholinesterase, the nicotinic acetylecholine receptor regulates the intensity and duration of the signal at the muscle.

Keywords: nicotinic acetylcholine receptors; ion channels; endplate; synaptic transmission

Figure 1.

Neuromuscular synapse.

Figure 2.

The triune receptor concept, describing neurotransmitter receptors as signal converters turning an extracellular signal into an intracellular effect.

Figure 3.

The nicotinic acetylcholine receptor. (a) Electron‐microscopic picture of the membrane bound receptor (left: longitudinal section; right: cross‐section showing the pentameric structure. (b) Schematic of the receptor protein showing the pentameric complex in its membrane environment (left) and a summary of the known functional domains (right): the helices depict the wall of the ion channel proper; the ellipses represent the location of the ligand‐binding sites at the interface between subunits. (c) Schematic representation of the transmembrane folding of the receptor subunits: M1–M4 represent the four membrane‐spanning sequences connected by extramembrane loops. N and C are the N‐ and C‐termini, respectively, of the polypeptide chain.

Figure 4.

Schematic representation of AChR aggregation in the postsynaptic membrane triggered by agrin. Synaptic differentiation involves at least five steps: (1) redistribution of AChRs, which are initially distributed on the entire myotube surface, to the subsynaptic part of the postsynaptic membrane; (2) increased transcription by synaptic nuclei of mRNAs encoding AChR subunits; (3) decreased transcription by extrasynaptic nuclei; (4) rearrangement of membrane cytoskeleton; (5) retrograde signal from the postsynaptic to the presynaptic side. ‘AAAA’ indicates polyadenylation. Reproduced from Hoch, , with permission from the author.

close

References

Axelsson J and Thesleff F (1959) A study of supersensitivity in denervated mammalian skeletal muscle. Journal of Physiology (London) 147: 178–193.

Colquhoun D and Sakmann B (1998) From muscle endplate to brain synapses: a short history of synapses and agonist‐activated ion channels. Neuron 20: 381–387.

Changeux J‐P and Edelstein S (1998) Allosteric receptors after 30 years. Neuron 21: 959–980.

Hoch W (1999) Formation of the neuromuscular junction; agrin and its unusual receptors. European Journal of Biochemistry 265: 1–10.

Hucho F, Tsetlin VI and Machold J (1996) The emerging three‐dimensional structure of a receptor: the nicotinic acetylcholine receptor. European Journal of Biochemistry 239: 539–557.

Katz B (1966) Nerve, Muscle, and Synapse. New York: McGraw‐Hill.

Laufer R and Changeux J‐P (1989) Activity dependent regulation of gene expression in muscle and neuronal cells. Molecular Neurobiology 3: 1–53.

Salpeter M and Loring RH (1985) Nicotinic acetylcholine receptors in vertebrate muscle: properties, distribution, and neural control. Progress in Neurobiology 25: 297–325.

Unwin N (1993) Nicotinic acetylcholine receptor at 9Å resolution. Journal of Molecular Biology 22: 1101–1124.

Vincent A, Newland C, Croxen R and Beeson D (1997) Genes at the junction – candidates for congenital myasthenic syndromes. Trends in Neurosciences 20: 15–22.

Further Reading

Shepherd GM (1994) Neurobiology. New York: Oxford University Press.

Siegel GJ, Agranoff BW, Albers RW, Fisher SK and Uhler MD (1999) Basic Neurochemistry, 6th edn. Philadelphia: Lippincott Raven.

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

* Required Field

How to Cite close
Hucho, Ferdinand(Apr 2001) Nicotinic Acetylcholine Receptors in Muscle. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000238]