acetylcholine

acetylcholine is a neurotransmitter released from nerve endings (terminals) in both the peripheral and the central nervous systems. It is synthesized within the nerve terminal from choline, taken up from the tissue fluid into the nerve ending by a specialized transport mechanism. The enzyme necessary for this synthesis (choline acetyltransferase) is formed in the nerve cell body and passes down the axon to its end, carried in the axoplasmic flow, the slow movement of intracellular substance (cytoplasm). Acetylcholine is stored in the nerve terminal, sequestered in small vesicles awaiting release.

When a nerve action potential reaches and invades the nerve terminal, a shower of acetylcholine vesicles is released into the junction (synapse) between the nerve terminal and the ‘effector’ cell which the nerve activates. This may be another nerve cell or a muscle or gland cell. Thus electrical signals are converted to chemical signals, allowing messages to be passed between nerve cells or between nerve cells and non-nerve cells. This process is termed ‘chemical neurotransmission’ and was first demonstrated, for nerves to the heart, by the German pharmacologist Loewi in 1921. Chemical transmission involving acetylcholine is known as ‘cholinergic’.

Acetylcholine acts as a transmitter between motor nerves and the fibres of skeletal muscle at all neuromuscular junctions. At this type of synapse, the nerve terminal is closely apposed to the cell membrane of a muscle fibre at the so-called motor end plate. On release, acetylcholine acts almost instantly, to cause a sequence of chemical and physical events (starting with depolarization of the motor endplate) which cause contraction of the muscle fibre. This is exactly what is required for voluntary muscles in which a rapid response to a command is required. The action of acetylcholine is terminated rapidly, in around 10 milliseconds; an enzyme (cholinesterase) breaks the transmitter down into choline and an acetate ion. The choline is then available for re-uptake into the nerve terminal.

These same principles apply to cholinergic transmission at sites other than neuromuscular junctions, although the structure of the synapses differs. In the autonomic nervous system these include nerve-to-nerve synapses at the relay stations (ganglia) in both the sympathetic and the parasympathetic divisions, and the endings of parasympathetic nerve fibres on non-voluntary (smooth) muscle, the heart, and glandular cells; in response to activation of this nerve supply, smooth muscle contracts (notably in the gut), the frequency of heart beat is slowed, and glands secrete. Acetylcholine is also an important transmitter at many sites in the brain at nerve-to-nerve synapses.

To understand how acetylcholine brings about a variety of effects in different cells it is necessary to understand membrane receptors. In post-synaptic membranes (those of the cells on which the nerve fibres terminate) there are many different sorts of receptors and some are receptors for acetylcholine. These are protein molecules that react specifically with acetylcholine in a reversible fashion. It is the complex of receptor combined with acetylcholine which brings about a biophysical reaction, resulting in the response from the receptive cell. Two major types of acetylcholine receptors exist in the membranes of cells. The type in skeletal muscle is known as ‘nicotinic’; in glands, smooth muscle, and the heart they are ‘muscarinic’; and there are some of each type in the brain. These terms are used because nicotine mimics the action of acetylcholine at nicotinic receptors, whereas muscarine, an alkaloid from the mushroom Amanita muscaria, mimics the action of acetylcholine at the muscarinic receptors.

Alan W. Cuthbert

See also autonomic nervous system; neurotransmitters.