O Cholinergic Receptors

There are two distinct receptor types for ACh that differ in composition, location, and pharmacological function and have specific agonists and antagonists. Cholinergic receptors have been characterized as nicotinic and muscarinic on the basis of their ability to be bound by the naturally occurring alkaloids nicotine and muscarine, respectively. Receptor subtypes that differ in location and specificity to agonists and antagonists have been identified for both the nicotinic and muscarinic receptors.

Nicotinic Receptors

Nicotinic receptors are coupled directly to ion channels and, when activated by Ach, mediate very rapid responses. Ion channels are responsible for the electrical excitability of nerve and muscle cells and for the sensitivity of sensory cells. The channels are pores that open or close in an all-or-nothing fashion on time scales ranging from 0.1 to 10 milliseconds to provide aqueous pathways through the plasma membrane that ions can transverse. Factors affecting selectivity of ion pores include both the charge and size of the ion. Ions in aqueous solution are hydrated. The water around the ion is characterized by the presence of two distinct water structures: a tightly bound, highly ordered layer immediately surrounding the ion and a second, less structured layer4 (Fig. 17.1). Ion transport through a channel requires some denuding of the surrounding water shell. The degree of organization of the water structure determines the energy required to remove the hydration

Figure 17.1 • Hydrated cation showing a highly structured shell of water around the cation (A), a less structured layer surrounding the inner water shell (B), and water in a "normal" state (C). (With permission from the author and the Royal Society of Chemistry.)

TABLE 17.1 Radii of Alkali and Alkali Earth Cations

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