6 Cholinergic neurotransmission
Acetylcholine is synthesized and stored in vesicles and released following activation of voltage-dependent calcium channels (Fig. 3.6.1). The entry of Ca2+ into preganglionic nerve terminals triggers the fusion of vesicles with the plasma membrane and release of acetylcholine into the ganglionic junction. This acetylcholine activates the nicotinic receptor (receptor-operated sodium channel) on the postjunctional neuronal membranes within the ganglion. The entry of Na+ into the postjunctional neuron triggers membrane depolarization, activation of voltage-dependent sodium channels and the propagation of an action potential along the length of the postganglionic nerve, culminating in the opening of voltage-dependent calcium channels in the terminal endings and the release of acetylcholine into the neuroeffector junction. The release of acetylcholine at neuroeffector sites (e.g. smooth muscle, exocrine glands) activates muscarinic receptors belonging to the G-protein-coupled receptor family. The pharmacological action of acetylcholine is short lived owing to its rapid metabolism by acetylcholinesterase into inactive acetic acid and choline. A variety of drugs can interfere with cholinergic neurotransmission at several sites along this pathway (Fig. 3.6.2).
Fig. 3.6.1 Parasympathetic transmission. CAT, choline acetyltransferase; AChE, acetylcholinesterase.
