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The Molecular Basis of Neurotransmission: Structure and Function of the Nicotinic Acetylcholine Receptor

  • Chapter
The Enzymes of Biological Membranes

Abstract

Acetylcholine was identified as the first neurotransmitter as a result of elegant experiments by Otto Loewi in 1921 who demonstrated that the vagus nerve liberates a substance that has an inhibitory effect on the rate of the heartbeat of an isolated frog heart. Loewi showed that this “vagus substance” could be transferred from the fluid filling the heart onto another heart and there reproduce the same inhibitory effect. He coined the term “humoral transmission” to describe this activity (Loewi, 1921). Subsequent experiments identified the “vagus substance” as acetylcholine. It became clear that acetylcholine, in addition to its influence on the heart, exerted a variety of pharmacologically distinct effects, which were classified by Sir Henry Dale (1934) as “muscarinic” and “nicotinic” actions, because some were mimicked best by muscarine and others by nicotine. Acetylcholine receptors with muscarinic ligand-binding properties are characterized by prolonged responses of slow onset which are mediated through nucleotide cyclases (for short reviews see Sokolovsky and Bartfai, 1981; Hartzell, 1982), whereas acetylcholine receptors with nicotinic-binding properties are characterized by rapid responses in which ligand binding regulates the opening and closing of a cation-specific channel through a conformational alteration in the molecule. Acetylcholine receptors at the neuromuscular junctions of striated muscle and at the synapses of fish electric organs (which are phylogenetically related to muscle tissue) are the best-studied nicotinic acetylcholine receptors and the subjects of this review.

One thing I have learned in a long life: that all our science, when measured against reality, is primitive and childlike; and yet it is the most precious thing we have.

Albert Einstein

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Anholt, R., Lindstrom, J., Montal, M. (1985). The Molecular Basis of Neurotransmission: Structure and Function of the Nicotinic Acetylcholine Receptor. In: Martonosi, A.N. (eds) The Enzymes of Biological Membranes. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4601-2_10

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