Acetylcholine

Abstract

From the discovery of ‘Vagusstoff’ (vagus substance) came a Nobel Prize and the sprouting of many neurological breakthroughs and insights into the chemical acetylcholine. Acetylcholine (ACh), a versatile synaptic compound, is evolutionarily conserved and present in all animals. The ancient role of acetylcholine in cell–cell communication and cellular modulation was expanded in metazoans to include neuron–neuron and neuro‐muscular signalling. ACh is widely expressed, present in the central nervous system (CNS), the peripheral nervous system (PNS) and in nonneuronal cells. Deficits in ACh‐mediated processes contribute to a variety of neuromuscular and neurodegenerative diseases, including myasthenia gravis and Alzheimer disease. Nicotine in tobacco products mimics acetylcholine's actions in the brain, causing nicotine dependence in smokers. The development of new experimental tools in the mammalian nervous system and studies of conserved mechanisms in invertebrate models have enhanced our understanding of acetylcholine function.

Key Concepts

  • Acetylcholine is an evolutionarily conserved signalling molecule.
  • Acetylcholine performs diverse functions in the central nervous system, peripheral nervous system and in nonneuronal cells.
  • Nicotine, toxins and insecticides target parts of acetylcholine pathways.
  • Dysfunctions in acetylcholine signalling underlie neuromuscular diseases such as myasthenia gravis and are associated with neurodegenerative diseases such as Alzheimer disease.
  • Invertebrate model systems offer experimental strengths to address lingering questions about neuronal and non‐neuronal mechanisms of acetylcholine function.

Keywords: acetylcholine; cholinergic neurons; neuromuscular disease; CNS; PNS; evolutionary conservation; cell–cell signalling; smoking; synapse

Figure 1. Acetylcholine synthesis, release, degradation and uptake pathways. Top insets, chemical pathways for acetylcholine biosynthesis through the enzyme choline acetyltransferase (ChAT) (left) and breakdown through acetylcholinesterase (AChE) (right).
Figure 2. Organisation of the conserved cholinergic gene locus in C. elegans, Drosophila and rat. Coordinated expression of both VAChT and ChAT is regulated through a common shared exon (green). Genes are not drawn to same scale. Adapted from Rand, J.B., et al. .
Figure 3. Acetylcholine receptor classes: ligand‐gated nicotinic receptors and muscarinic G protein‐coupled receptors.
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Further Reading

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Oliver, Devyn, and Francis, Michael M(Sep 2020) Acetylcholine. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0029192]