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 system
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 system
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).
Neurochemical transmission
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).
