Introduction

NS

CNS PNS

Brain Spinal Cord SNS ANS

Sympathetic Parasympathetic Enteric

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Autonomic NS
 Operates involuntarily on reflex control
 Functions to maintain the constancy of the internal
environment (homeostasis)
 Innervates three types of effector cells
1. Smooth muscle
2. Cardiac muscle
3. Exocrine glands
Somatic NS innervates skeletal muscle
 Voluntary control of skeletal muscle

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Anatomical differences: ANS vs
SNS
Neurons between CNS and effector cells
Two neurons in ANS ( preganglionic and post ganglionic
neuron)
Only one neuron in somatic NS
Synaptic junctions in ANS occur in ganglia which lie out side
the cerebrospinal axis while no such structures occur in
somatic NS.
While efferent neurons in somatic NS are myelinated,
generally postsynaptic autonomic neurons are non myelinated.

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The ANS lends itself to division on anatomic grounds
into two major portions
Sympathetic nervous system (thoracolumbar)
Parasympathetic nervous system (craniosacral)
¿¿¿Enteric nervous system???

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Sympathetic vs Parasympathetic
Location of cell body of preganglionic neuron
 From brain stem and sacral segment of the spinal cord in
Parasympathetic
 From thoracic and lumbar segments of the spinal cord in
Sympathetic
Location of ganglia
 Close to effector cell in parasympathetic
 Generally close to vertebral column in sympathetic
Ratio of preganglionic to postganglionic neurons
 Almost one to one in parasympathetic
 One to more than 20 in sympathetic

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 Physiology of ANS
The ANS controls smooth muscle, exocrine secretions,
and rate & force of the heart
Sympathetic and parasympathetic systems have
opposing actions in some situations (e.g. control of
heart rate), but not in others (e.g. salivary glands).
Sympathetic activity increases in
stress ('fight or flight‘), whereas PNS
activity predominates ‘rest & digest’.
Both systems exert a continuous
physiological control of specific
organs under normal conditions
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 Fight or flight vs. Rest and Digest
ORGAN SYMP. PARASYMP.
Heart  rate and force  rate and force
Blood vessels mostly constriction no effect
(dilates some skeletal
muscle arterioles and
some veins)
Airway smooth muscle dilatation constriction
GI tract  motility  motility
Male sex organs ejaculation erection
Eye (pupil) dilatation constriction
Sailvary glands secretion secretion
Liver glycogenolysis no effect
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Blood Vessels:
Express , , dopamine (DA), histamine and M
receptors.
More complex
 Sympathetic- NE (, 1), epinephrine (1, 2, 1, 2)
and dopamine (DA) are released
 1 vasoconstricts vessels, mainly at the arterioles
 2 vasodilates skeletal vessel
DA- three different mechanisms, concentration-
dependent
 Low dose DA- stimulates D1
 Mid-dose DA- stimulates 2
 High Dose DA- stimulate 1 receptors

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Parasympathetic:
Smooth muscles of blood vessel lack muscarinic
receptors
Endothelial cells contain M3 receptor
Nitric oxide synthase dependent relaxation of smooth
muscle
Eye
Ciliary Muscle
Sympathetic: Ciliary epithelium produces aqueous
humor through  receptors stimulation
Parasympathetic: pulls on the trabecular meshwork to
open the canal of schlemm and drain the fluid
 Accommodation of focus for near vision
 Cyclospasm

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Pupil
 Sympathetic activity :mydriasis (1)
 Parasympathetic activity : miosis(m3)

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ANS Neurotransmission
Neurotransmission in the PNS occurs at three major sites:
Autonomic ganglia
Autonomic neuroeffector junctions
All somatic motor end plates on skeletal muscle.
Ach and NE are the major autonomic neurotransmitters
 Cholinergic neurons
 Cholinoreceptors
 Cholinomimetic Ach
 Cholinoreceptor antagonists

 Adrenergic neurons

 Adrenoceptors

 Adrenomimetic (sympathomimetic NE
 Adrenoceptor antagonists

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Receptors
Cholinoceptor
Two types (nicotinic and muscarinic)
Nicotinic receptors
Ligand-gated ion channels and fall into three main
classes: ganglionic (Nn), muscle (Nm) and CNS
subtypes
Muscarinic receptors
G-protein coupled receptors
Five types: M1, M2, M3, M4, and M5

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M1 (Neural)
Found mainly in the CNS, peripheral neurons and
gastric parietal cells
M2 (Cardiac)
Found in the heart & presynaptic terminals of peripheral
and central neurons
M3 (Glandular)
Occur on exocrine glands, smooth muscles, endothelial
cells and CNS
M4 and M5
Found in the CNS
All mAChRs are activated by acetylcholine and
blocked by atropine
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Adrenoceptors
Alpha1 (dominantly located in blood vessels except
blood vessels of skeletal muscle)
Alpha2 (dominantly located presynaptically)
Beta1 (dominantly located in heart)
Beta2 (dominantly located in bronchi, blood vessels of
skeletal muscle and uterine wall)
Beta3 (dominantly found in adipose tissue)

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Summary

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Steps in neurotransmission
5 key steps :
1. Synthesis of neurotransmitter from precursor
molecules.
2. Storage of neurotransmitter in vesicles
3. Release of neurotransmitter by exocytosis, which
requires Ca2+ influx.
4. Termination of action of neurotransmitter either by
enzyme hydrolysis or by reuptake mechanism
5. Recognition of neurotransmitter by receptors

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Cholinergic Transmission
Choline is taken from plasma (ratelimiting step in ACh
synthesis
It is inhibited by hemicholinium
Ach is synthesized by choline acetyltransferase(transfer of
an acetyl group from acetylcoenzyme A to choline)
Ach then taken into synaptic vesicles via a proton
antiporter,
which can be inhibited by vesamicol
Upon the arrival of an action potential Ach released by
exocytosis
Blocked by botulinum toxin
The action of Ach is terminated acetylcholinesterase
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Adrenergic Transmission
Tyrosine in the bloodstream is taken up into nerves
and converted into catecholamine
Tyrosine hydroxylase (tyrosine to dopa) is the
ratelimiting step in NE
Inhibited by metyrosine (α-methyl-p-tyrosine).
Dopa to dopamine is catalysed by dopa decarboxylase
Dopamine-ß-hydroxylase is located in synaptic
vesicles converts dopamine to noradrenaline

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After its synthesis is over it is stored in vesicle
and released when action potential is generated.
The action of noradrenaline or adrenaline is
terminated by
1. Reuptake into nerve terminals by NET (α2)
 Uptake 1 or reuptake 1
2. Dilution by diffusion out of the junctional
cleft and uptake at extraneuronal sites ; and
3. Metabolic transformation
 Monoamine oxidase (MAO)
 Catechol-O-methyltransferase (COMT).

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Presynaptic and postsynaptic
modulation
Negative feedback control is also found at the
presynaptic level of autonomic function
Presynaptic release of transmitters depends
 Transmitter themselves and
 Chemicals released by other tissues into the synapse
Presynaptic receptors that respond to the primary
transmitter substance ….autoreceptors (α2)
Autoreceptors are usually inhibitory

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Example Ach inhibits its own release and NE
inhibits Ach and its own release
Heterotropic inhibition is when a neurotransmitter
affects the release of another
Homotropic inhibition is when a transmitter, by
binding to a presynaptic autoreceptors, affects its own
release from the nerve terminal

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Postsynaptic regulation can be considered from
two perspectives
Modulation by the history of activity
 Up-or down-regulation
 Denervation supersensitivity

 Desensitization

Modulation by other temporally associated

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Binding of an appropriate ligand to a neuronal
nicotinic (NN) acetylcholine receptor
Resulting in fast excitatory postsynaptic potential
(EPSP)
Followed by slow inhibitory postsynaptic potential
(IPSP)
Due to hyperpolarization involves opening and closing
of potassium channels by M2 and M1cholinoceptors

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Integration of Cardiovascular Function
Autonomic reflexes are particularly important in
understanding CVS responses to autonomic drugs
The main controllable variable is mean arterial
pressure ( BP= CO * SVR )
Change evoke powerful homeostatic secondary
responses
May be sufficient to reduce the change in mean arterial
pressure and to reverse the drug's effects on heart rate

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The net effect of ordinary pressor doses of
norepinephrine in a normal subject
A marked increase in peripheral vascular
resistance, an increase in mean arterial
pressure, and a consistent slowing of heart rate
 Feedback baroreceptor response to increased mean
arterial pressure causes
 Decreased sympathetic outflow to the heart and

 A powerful increase in parasympathetic (vagus

nerve) discharge at the cardiac pacemaker

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Autonomic and hormonal control of cardiovascular
function

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