The Autonomic Nervous System
The autonomic nervous system (ANS) provides the efferent pathway for the involuntary control of most organs, excluding the motor control of skeletal muscle (Chapters 12 and 13). The ANS provides the effector arm for homeostatic reflexes (e.g. control of blood pressure), and allows the integration and modulation of function by central mechanisms in the brain in response to environmental and emotional stimuli (e.g. exercise, thermoregulation, ‘fight or flight’). Figure 7a shows a simplified schematic diagram of the ANS, and Figure 8b its actions on major organs.
The ANS is divided into sympathetic and parasympathetic systems. Both contain preganglionic neurones originating in the central nervous system that synapse with non-myelinated postganglionic neurones in the peripheral ganglia; postganglionic neurones innervate the target organ or tissue (Fig. 7a,b). Preganglionic neurones of both sympathetic and parasympathetic systems release acetylcho- line in the synapse, which acts on cholinergic nicotinic receptors on the postganglionic fibre. The postganglionic neurotransmitters and receptors depend on the system and organ (see below). Parasympathetic peripheral ganglia are generally found close to or in the target organ, whereas sympathetic ganglia are largely located in two sympathetic chains either side of the vertebral column (paravertebral ganglia), or in diffuse prevertebral ganglia of the visceral plexuses of the abdomen and pelvis (Fig. 7a). Sympathetic postganglionic neurones are therefore generally long, whereas parasympathetic neurones are generally short. An exception is the sympathetic innervation of the adrenal gland, where preganglionic neurones directly innervate the adrenal medulla.
The sympathetic system is more pervasive than the parasympathetic; where an organ is innervated by both systems, they often act antagonistically (Fig. 7b). However, there is a high degree of central coordination, so that an increase in sympathetic activity to an organ is commonly accompanied by a decrease in parasympathetic activity. Sympathetic and parasympathetic activity may modulate different functions in the same organ (e.g. genital organs). In loose terms, the sympathetic system might be said to coordinate ‘flight or fight’ responses, and the parasympathetic system ‘rest and digest’ responses.
Sympathetic preganglionic neurones originate in the lateral horn of segments T1–L2 of the spinal cord, and exit the cord via the ventral horn (Fig. 7c) on their way to the paravertebral or prevertebral ganglia. Sympathetic postganglionic neurones terminate in the effector organs, where they release noradrenaline (norepinephrine). Noradrenaline and adrenaline (epinephrine), which is released by the adrenal medulla, are catecholamines, and activate adrenergic receptors, which are linked via G-proteins to cellular effector mechanisms. There are two main classes of adrenergic receptor, α and β, and these are further subdivided into several subtypes (e.g. α1, α2, β2, β2). Noradren- aline and adrenaline are equally potent on α1-receptors, which are linked to Gq-proteins and are commonly associated with smooth muscle contraction (e.g. blood vessels). The α2-receptors are Gi/o- protein linked and are often inhibitory. All β-receptors are linked to Gs-protein and activate adenylyl cyclase to make cyclic adenosine monophosphate (cAMP). Noradrenaline is more potent at β1-receptors and adrenaline is more potent at β2-receptors. The activation of β-receptors is associated with the relaxation of smooth muscle (e.g. blood vessels, airways), but it increases heart rate and force (Fig. 7b). A few sympathetic neurones release acetylcholine at the effector (e.g. sweat glands), and are thus known as sympathetic cholinergic neurones.
Parasympathetic preganglionic neurones originate in the brain stem, from which they run in cranial nerves III, VII, IX and X (vagus), and also from the second and third sacral segments of the spinal cord (Fig. 7a). Parasympathetic postganglionic neurones release acetylcholine, which acts on cholinergic muscarinic receptors. Parasympathetic activation causes secretion in many glands (e.g. bronchial mucous glands), and either contraction (e.g. bladder detrusor) or relaxation (e.g. bladder internal sphincter) of smooth muscle, although it has little effect on blood vessels. Notable exceptions, however, include vasodilatation in the penis and clitoris with subsequent erection (Chapter 51).
Action potentials (APs) in incoming neurones are transmitted by the release of neurotransmitters that bind to receptors on the postganglionic neurone or effector tissue. Between neurones (e.g. in ganglia), this occurs within a classical synapse, where the axon terminates in a bulbous swelling or bouton separated from the target by a narrow (10–20 nm) synaptic cleft (Fig. 7di). Postganglionic neurones branch repeatedly and have numerous boutons along their length, forming varicosities (e.g. see blood vessel in Fig. 7a). The boutons may either be close (∼20 nm) to the effector membrane, allowing fast and specific delivery of the signal, or at some distance (100–200 nm), allowing a more distributed but slower effect. The mechanisms of neurochemical transmission are similar, and although the text below and Fig. 7di–iv refer to synapses, the same principles apply.
Synthetic enzymes are transported down the axon into the bouton, where they synthesize neurotransmitter (acetylcholine, noradrenaline) from precursors transported into the bouton. The neurotransmitter is stored in 50-nm vesicles (Fig. 7di). The arrival of an AP at the nerve ending causes an influx of Ca2+, the fusion of vesicles with the membrane and the release of neurotransmitter; this binds to postsynaptic receptors and activates the response. Neurotransmitter release can be suppressed by feedback onto presynaptic inhibitory receptors (α2-receptors for adrenergic synapses) (Fig. 7dii). Neurotransmitters must be removed at the end of activation. In cholinergic synapses, cholinesterase rapidly breaks down acetylcholine into choline and acetate, which are recycled; some may escape into interstitial fluid (overflow) (Fig. 7diii). In adrenergic synapses, most noradrenaline is rapidly taken up again by the nerve ending via an adenosine tri- phosphate (ATP)-dependent transporter called uptake-1; recovered noradrenaline is recycled. Some facilitated diffusion (uptake-2) also occurs into smooth muscle. Excess noradrenaline and sympathomimetic amines, such as tyramine (found in some foodstuffs), are metabolized in the neurone by mitochondrial monoamine oxidase (MAO). Noradrenaline and other catecholamines that enter the circulation are metabolized sequentially by catechol-O-methyl transferase (COMT) and MAO (Fig. 7div).