chapter

2 Neurophysiology

I. AUTONOMIC NERVOUS SYSTEM (ANS)

■ is a set of pathways to and from the central nervous system (CNS) that innervates and
regulates smooth muscle, cardiac muscle, and glands.
■ is distinct from the somatic nervous system, which innervates skeletal muscle.
■ has three divisions: sympathetic, parasympathetic, and enteric (the enteric division is dis-
cussed in Chapter 6).

A. Organization of the ANS (Table 2.1 and Figure 2.1)

1. Synapses between neurons are made in the autonomic ganglia.
a. Parasympathetic ganglia are located in or near the effector organs.
b. Sympathetic ganglia are located in the paravertebral chain.
2. Preganglionic neurons have their cell bodies in the CNS and synapse in autonomic
ganglia.
■ Preganglionic neurons of the sympathetic nervous system originate in spinal cord seg-
ments T1–L3 or the thoracolumbar region.
■ Preganglionic neurons of the parasympathetic nervous system originate in the nuclei of
cranial nerves and in spinal cord segments S2–S4 or the craniosacral region.
3. Postganglionic neurons of both divisions have their cell bodies in the autonomic ganglia
and synapse on effector organs (e.g., heart, blood vessels, sweat glands).
4. Adrenal medulla is a specialized ganglion of the sympathetic nervous system.
■ Preganglionic fibers synapse directly on chromaffin cells in the adrenal medulla.
■ The chromaffin cells secrete epinephrine (80%) and norepinephrine (20%) into the cir-
culation (see Figure 2.1).
■ Pheochromocytoma is a tumor of the adrenal medulla that secretes excessive amounts
of catecholamines and is associated with increased excretion of 3-methoxy-4-hydroxy-
mandelic acid (VMA).

B. Neurotransmitters of the ANS

■ Adrenergic neurons release norepinephrine as the neurotransmitter.
■ Cholinergic neurons, whether in the sympathetic or parasympathetic nervous system,
release acetylcholine (ACh) as the neurotransmitter.
■ Nonadrenergic, noncholinergic neurons include some postganglionic parasympathetic neu-
rons of the gastrointestinal tract, which release substance P, vasoactive intestinal peptide
(VIP), or nitric oxide (NO).

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 Chapter 2 Neurophysiology 33

t a b l e 2.1 Organization of the Autonomic Nervous System

Characteristic Sympathetic Parasympathetic Somatic*
Origin of preganglionic Nuclei of spinal cord Nuclei of cranial nerves
nerve segments T1–T12; III, VII, IX, and X;
L1–L3 (thoracolumbar) spinal cord segments
S2–S4 (craniosacral)
Length of preganglionic Short Long
nerve axon
Neurotransmitter in ACh ACh
ganglion
Receptor type in Nicotinic Nicotinic
ganglion
Length of postganglionic Long Short
nerve axon
Effector organs Smooth and cardiac Smooth and cardiac Skeletal muscle
muscle; glands muscle; glands
Neurotransmitter in Norepinephrine (except ACh ACh (synapse is
effector organs sweat glands, which neuromuscular
use ACh) junction)
Receptor types in α1, α2, β1, and β2 Muscarinic Nicotinic
effector organs
*
Somatic nervous system has been included for comparison. ACh = acetylcholine.

CNS Effector organ

Postganglionic
Preganglionic
Parasympathetic

ACh ACh Muscarinic

Nicotinic receptor
receptor (NN)

Preganglionic Postganglionic
Sympathetic

ACh Nicotinic Norepinephrine* α1, α2, β1, β2

receptor (NN) receptors

Epinephrine (80%)
Adrenal Norepinephrine (20%)
ACh Adrenal gland
Nicotinic
receptor

Skeletal
Somatic muscle

ACh Nicotinic
receptor (NM)
*Except sweat glands, which use ACh.
FIGURE 2.1 Organization of the autonomic nervous system. ACh = acetylcholine; CNS = central nervous system.
34 BRS Physiology

t a b l e 2.2 Signaling Pathways and Mechanisms for Autonomic Receptors

Receptor Location G Protein Mechanism
Adrenergic
α1 Smooth muscle Gq ↑ IP3 /Ca2+
α2 Gastrointestinal tract Gi ↓ cAMP

β1 Heart Gs ↑ cAMP

β2 Smooth muscle Gs ↑ cAMP

Cholinergic
NM (N1) Skeletal muscle — Opening Na+/K+ channels
NN (N2) Autonomic ganglia — Opening Na+/K+ channels
M1 CNS Gq ↑ IP3 /Ca2+
M2 Heart Gi ↓ cAMP

M3 Glands, smooth muscle Gq ↑ IP3 /Ca2+

IP3 = inositol 1,4,5-triphosphate; cAMP = cyclic adenosine monophosphate.

C. Receptor types in the ANS (Table 2.2)

1. Adrenergic receptors (adrenoreceptors)
a. a1 Receptors
■ are located on vascular smooth muscle of the skin and splanchnic regions, the gas-
trointestinal (GI) and bladder sphincters, and the radial muscle of the iris.
■ produce excitation (e.g., contraction or constriction).
■ are equally sensitive to norepinephrine and epinephrine. However, only norepi-
nephrine released from adrenergic neurons is present in high enough concentra-
tions to activate α1 receptors.
■ Mechanism of action: Gq protein, stimulation of phospholipase C and increase in
inositol 1,4,5-triphosphate (IP3) and intracellular [Ca2+].
b. a2 Receptors
■ are located on sympathetic postganglionic nerve terminals (autoreceptors), plate-
lets, fat cells, and the walls of the GI tract (heteroreceptors).
■ often produce inhibition (e.g., relaxation or dilation).
■ Mechanism of action: Gi protein, inhibition of adenylate cyclase and decrease in cyclic
adenosine monophosphate (cAMP).
c. b1 Receptors
■ are located in the sinoatrial (SA) node, atrioventricular (AV) node, and ventricular
muscle of the heart.
■ produce excitation (e.g., increased heart rate, increased conduction velocity,
increased contractility).
■ are sensitive to both norepinephrine and epinephrine, and are more sensitive than
the α1 receptors.
■ Mechanism of action: Gs protein, stimulation of adenylate cyclase and increase in cAMP.
d. b2 Receptors
■ are located on vascular smooth muscle of skeletal muscle, bronchial smooth muscle,
and in the walls of the GI tract and bladder.
■ produce relaxation (e.g., dilation of vascular smooth muscle, dilation of bronchioles,
relaxation of the bladder wall).
■ are more sensitive to epinephrine than to norepinephrine.
■ are more sensitive to epinephrine than the α1 receptors.
■ Mechanism of action: same as for β1 receptors.
 Chapter 2 Neurophysiology 35

2. Cholinergic receptors (cholinoreceptors)

a. Nicotinic receptors
■ are located in the autonomic ganglia (N ) of the sympathetic and parasympathetic
N
nervous systems, at the neuromuscular junction (NM), and in the adrenal medulla (NN).
The receptors at these locations are similar, but not identical.
■ are activated by ACh or nicotine.
■ produce excitation.
■ are blocked by ganglionic blockers (e.g., hexamethonium) in the autonomic ganglia,
but not at the neuromuscular junction.
■ Mechanism of action: ACh binds to α subunits of the nicotinic ACh receptor. The nic-
otinic ACh receptors are also ion channels for Na+ and K+.
b. Muscarinic receptors
■ are located in the heart (M ), smooth muscle (M ), and glands (M ).
2 3 3
■ are inhibitory in the heart (e.g., decreased heart rate, decreased conduction velocity
in AV node).
■ are excitatory in smooth muscle and glands (e.g., increased GI motility, increased
secretion).
■ are activated by ACh and muscarine.
■ are blocked by atropine.
■ Mechanism of action:

(1) Heart SA node: Gi protein, inhibition of adenylate cyclase, which leads to opening
of K+ channels, slowing of the rate of spontaneous Phase 4 depolarization, and
decreased heart rate.
(2) Smooth muscle and glands: Gq protein, stimulation of phospholipase C, and increase
in IP3 and intracellular [Ca2+].
3. Drugs that act on the ANS (Table 2.3)

t a b l e 2.3 Prototypes of Drugs that Affect Autonomic Activity

Type of Receptor Agonist Antagonist

Adrenergic
α1 Norepinephrine Phenoxybenzamine
Phenylephrine Phentolamine
Prazosin

α2 Clonidine Yohimbine

β1 Norepinephrine Propranolol
Isoproterenol Metoprolol
Dobutamine

β2 Isoproterenol Propranolol
Albuterol Butoxamine
Cholinergic
Nicotinic ACh Curare (neuromuscular
Nicotine junction N1
Carbachol receptors)
Hexamethonium (ganglionic
N2 receptors)
Muscarinic ACh Atropine
Muscarine
Carbachol
ACh = acetylcholine.
36 BRS Physiology

t a b l e 2.4 Effect of the Autonomic Nervous System on Organ Systems

Sympathetic Sympathetic Parasympathetic Parasympathetic

Organ Action Receptor Action Receptor

Heart ↑ heart rate β1 ↓ heart rate M2

↑ contractility β1 ↓ contractility (atria) M2
↑ AV node conduction β1 ↓ AV node conduction M2
Vascular smooth Constricts blood α1 —
muscle vessels in skin;
splanchnic
Dilates blood vessels β2 —
in skeletal muscle
Gastrointestinal tract ↓ motility α2, β2 ↑ motility M3
Constricts sphincters α1 Relaxes sphincters M3
Bronchioles Dilates bronchiolar β2 Constricts bronchiolar M3
smooth muscle smooth muscle
Male sex organs Ejaculation α Erection M
Bladder Relaxes bladder wall β2 Contracts bladder wall M3
Constricts sphincter α1 Relaxes sphincter M3
Sweat glands ↑ sweating M (sympathetic —
cholinergic)
Eye
Radial muscle, iris Dilates pupil (mydriasis) α1 —
Circular sphincter — Constricts pupil (miosis) M
muscle, iris
Ciliary muscle Dilates (far vision) β Contracts (near vision) M
Kidney ↑ renin secretion β1 —
Fat cells ↑ lipolysis β1 —

AV = atrioventricular; M = muscarinic.

D. Effects of the ANS on various organ systems (Table 2.4)

E. Autonomic centers—brain stem and hypothalamus

1. Medulla
■ Vasomotor center
■ Respiratory center
■ Swallowing, coughing, and vomiting centers
2. Pons
■ Pneumotaxic center
3. Midbrain
■ Micturition center
4. Hypothalamus
■ Temperature regulation center
■ Thirst and food intake regulatory centers

II. SENSORY SYSTEMS

A. Sensory receptors—general
■ are specialized epithelial cells or neurons that transduce environmental signals into neural
signals.