Excitable Tissue:

Nerve
 Nerve Tissue
Two principal cell types that make up the NS are
neurons and neuroglial cells
Neurons are functional units of the NS
Neurons are specialized for the generation and
transmission of nerve impulse.
Functions of neurons includes:
Sensory function
Generation of thought
Storage of memory
Integrates idea
Coordinates muscular activities

2
The Neuroglia
• The neuroglia are non excitable cells found in association with
neurons.
• They provide supporting functions to the nervous system.
They include:
Microglia:- specialized macrophages capable of phgocytosis and
protecting the CNS.
Astrocytes:- Provide nourishment to the CNS
Interconnectes axons with blood vessels
Make up the BBB
Oligodendrocytes:- are cells that coat axons of in the CNS and their
cell membrane is called myelin sheath
Ependymal cells:- line the cavity of the CNS and make up the walls
of the ventricles. Secrete CSF.
Schwann cells:- coat axons of the PNS
3
Neuroglia

4
 Neuroglia
• Outnumber neurons by about 20x
• Five types of supporting cells
– Four of them are found in the CNS:
1. Astrocytes
• Star-shaped, abundant, and
versatile
• Involved in the formation of the
blood brain barrier
• Function in nutrient transfer
• Interconnect blood vessels and
nerve fibers.
5
 Neuroglia
2. Microglia
• Specialized immune cells that
act as the macrophages of the
CNS
3. Ependymal Cells
• line the cavity of the CNS and
make up the walls of the
ventricles.
• Secrete CSF.
• Some are ciliated which
facilitates the movement of
cerebrospinal fluid
6
 Neuroglia

4. Oligodendrocytes
• Produce the myelin
sheath which
provides the electrical
insulation for certain
neurons in the CNS

7
 Neuroglia

5. Schwann cells
• Form myelin sheaths
around the larger nerve
fibers in the PNS.
• Vital to neuronal
regeneration

8
 Neurons: Functional structures
• Neurons are functional and structural units of
the nervous system.
• A neuron has three distinct parts. These are:
Cell body
Dendrites
Axon
• They are special to conduct information from
one part of the body to another
• There are many, many different types of
neurons but most have certain structural and
functional characteristics in common:
– Cell body (soma)
– One or more specialized, slender processes
(axons/dendrites)
– An input region (dendrites/soma)
– A conducting component (axon)
– A secretory (output) region (axon terminal)
9
Neuronal Processes
• Axons: myelinated/unmylinated
• Most neurons have a single
axon – a long (up to 1.5 mt)
process designed to convey info
away from the cell body.
• Originates from a special region
of the cell body called the axon
hillock.
• Transmit APs from the soma
toward the end of the axon
where they cause NT release.
• Often branch lightly, forming
collaterals.
10
Axons: myelinated/unmyelinated
• Axolemma = axon plasma membrane.
• Surrounded by a myelin sheath, a
wrapping of lipid which:
– Protects the axon and electrically
isolates it
– Increases the rate of AP transmission
• The myelin sheath is made by
oligodenrocytes in the CNS and by
Schwann cells in the PNS.
• Interspersed along the axon are gaps
where there is no myelin – these are
nodes of Ranvier.
• In the PNS, the exterior of the Schwann
cell surrounding an axon is the
neurilemma

11
Functional classification of neurons
There are three classes:
1. Sensory (afferent) neurons conduct impulses
from periphery to the center
2. Motor neurons (efferent) – conduct impulses
from CNS to the periphery
3. Interneurons (association neurons,
Integrative/interneurons) – conduct impulses
from sensory area to motor area.

12
 Classification of nerve fibers:
(myelination, rate of conduction, and diameter)
1. Type Aά Fibers
• They are myelinated fibers
• Function: Motor to the 4. Type B fibers
skeletal muscle
• Diameter: 10-20 µm • Preganglionic autonomic
• Conduction velocity: 60- fibers
120m/s • Myelinated
2. Type Aβ Fibers • Diameter: 2-6 µm
• Myelinated fibers • Conduction velocity: 6-
• Motor function
30m/s
• Diameter: 5-10 µm
• Conduction velocity: 30-60 5. Type C fibers
m/s • Post ganglionic fibers
3. Type Aσ and Aγ Fibers • Unmyelinated
• Myelinated • Diameter: 0.5- 2µm
• Motor in function • Conduction velocity: 0.5-
• Diameter: 1-6 µm 2m/s 13
• Conduction velocity: 6-30 m/s
Soma
Contains nucleus plus most
normal organelles.
Contains a very active and
developed rough endoplasmic
reticulum which is responsible
for the synthesis of NTs.
The neuronal rough ER is
referred to as the Nissl body. In the soma above, notice the small black
Contains many bundles of circle. It is the nucleolus, the site of
protein filaments (neurofibrils) ribosome synthesis. The light circular
which help maintain the shape, area around it is the nucleus. The
structure, and integrity of the mottled dark areas found throughout the
cell. cytoplasm are the Nissl substance.

14
Soma, cont’d

 Contain multiple
mitochondria.
 Acts as a receptive service
for interaction with other
neurons.
 Most soma are found in the
bony surroundings of the
CNS.
 Clusters of soma in the
CNS are known as nuclei.
 Clusters of somata in the
PNS are known as ganglia. 15
Resting membrane potential
All cells have a voltage difference across their plasma membrane.
This is called membrane potential.
The membrane potential (VM) at rest is called resting membrane
potential (RMP)
At rest, there are electropositivity out and electronegativity inside
the cell membrane of the neuron.
The RMP of a typical neuron is -90 mv

16
What are the causes of the RMP?
1. An outward diffusion of K+ through K+ leak channels.
The is very high concentration of Na+ in the ECF while
the is very high concentration of K+ in the ICF. As a result,
K+ is constantly leaking out of the cell.
2. The Na+-K+ ATP ase is constantly pumping 3 Na+ ions
outward and 2 K+ ions inward for every ATP used. Thus
more positive charge is leaving than entering.
3. There are negatively charged non-diffusible proteins within
the ICF that cannot travel through the membrane.
What this adds up to is the fact that the inside of the cell is negative
with respect to the outside.
The interior has less positive charge than the exterior.

17
 Classification of Ion Channels
I. Leak channel: are always open,
no gate on it. Ca+ Cahannels are the
II. Gated Channels: they have
gates following:
Na+ channels 1. Voltage- gated Ca+ channels
There are three major types
1. Na+ leak channels with subtypes
2. Voltage-gated Na+ channels L- type Ca+- gated channels
3. Ligand (chemical –gated) Na+ T- type Ca+- gated channels
channels N-type Ca+- gated channels
K+ Channels
2. Ligand- gated Ca+- channels
There are four major classes:
1. K+- leak channels
3. G- protein-gated Ca+- gated
2. Voltage-gated K+ channels channels
3. Ligand- gated K+ channels
4. G-prorein- gated K+ channels
18
Generation of Action Potential
• An immediate change of the RMP into depolarization that is
followed by reestablishment of the RMP (repolarization) is called
action potential or nerve impulse.
If RMP changes from -90 mv to threshold level (-75 mV), →voltage
gated Na+ channels open and → Na+ influx → depolarization. Na+
channels become inactivated soon.
Opening of voltage gated K+ channels →K+ efflux → repolarization.

19
 Action Potentials
• If VM reaches threshold, Na+ channels
open and Na+ influx ensues,
depolarizing the cell and causing the
VM to increase.
• This is the rising phase of an AP.
• Eventually, the Na+ channel will have
inactivated and the K+ channels will
be open.
• Now, K+ effluxes and repolarization
occurs.
• This is the falling phase.
– K+ channels are slow to open and
slow to close.
-90 mv
– This causes the VM to take a brief
dip below resting VM.
– This dip is the undershoot and is
an example of hyperpolarization.

20
 Conduction of Action Potential (AP)

• If an AP is generated at the axon hillock, it will

travel all the way down to the synaptic knob.
• The manner in which it travels depends on
whether the neuron is myelinated or unmyelinated.
• Unmyelinated neurons undergo the
Sweeping/continuous conduction of an AP
whereas
• Myelinated neurons undergo jumping/saltatory
conduction of an AP.

21
 Neurotransmitter Removal
• Why do we want to remove ACh
from the
neuromuscular junction?
• How was ACh removed from
the NMJ?

• NTs are removed from the synaptic

cleft via:
– Enzymatic degradation
– Diffusion
– Reuptake

22
Properties of synaptic transmission
1. Unidirectional conduction
2. Synaptic delay (0.5 -1.0m/s)
3. Fatigue -↓in response of postsynaptic neurons after
repetitive stimulation by the presynaptic neurons
4. Synaptic potentiation (facilitation):– persistence of out put
signals after the stoppage of in put signal
5. pH
Alkalosois ↑ Synaptic transmission
Acidosis ↓ Synaptic transmission
6. Hypoxia ↓ Synaptic transmission
7. Synaps is a target for the action of several groups of drugs
 Caffeine, theophylline, theobromine ↑Synaptic
transmission
Strychinine ↑ Synaptic transmission
1. Hypnotics, anesthtics, tranquilizers ↓ Synaptic
transmission 23
 Classes of neurotransmitters
Classes Neurotransmitters Receptors Distribution,
role
I Acetylcholine (Ach) Nicotinic receptors Excitatory in
Muscarinic receptors CNS, PNS
II Adrenaline, nor-adrenaline α and β adrenoreceptors Excitatory
Amines Dopamine Dopaminergic Rs: A, B Inhibitory in BG
Histamine Histaminergic Rs: H1 & 2 Excitatory
III GABA (γ-amino butyric GABA-A and B receptors Inhibitory in BG
Amino acid) Glycine receptors Inhibitory
Acids Glycine NMDA receptors Excitatory
Aspartate NMDA receptors Excitatory
Glutamate
IV Hypothalamic hormones, Hormone receptors Stimulatory or
Polypep pituitary hormones, ANG-II inhibitory
V Nitric oxide Memory 24
 PHYSIOLOGY OF MUSCLE
• Muscle is the fleshy organ of the body that converts potential
energy of food into mechanical energy.
• Muscle cells have a special capacity to utilize chemical energy to
produce force and movt that enable us to produce speech
and to manipulate objects around us.
•Accounts 40% of the BW

Types of muscles: 3 types

•Skeletal/voluntary muscles
Located attached to bones & moves skeleton
They are elongated, cylindrical and multinucleated cells,
They are striated muscle
They are voluntary muscle, controlled by SNS
Types of muscles
• Cardiac muscle:
– muscle of the heart
– They are striated
– They are involuntary, controlled by ANS, drugs and
hormones
– Have the property of autorhythmicity and syncytium
• Smooth muscles
– Located in the wall of hallow organs (GIT, blood vessels,
uterus, u-bladder, Iris)
– They have non-striated appearance, mononucleated cells
– involuntary muscle, controlled by ANS, drugs and
hormones
– Have the property of autorhythmicity and syncytium
Types of muscles
Muscle tissue
Characteristics of muscle:
• Excitability - responds to stimuli (e.g., nervous
impulses)
• Contractility - able to shorten in length
• Extensibility - stretches when pulled
• Elasticity - tends to return to original shape & length
after contraction or extension
Functions of muscle:
• Motion
• Maintenance of posture
• Heat production
 Structural organization of skeletal muscle
Entire muscle

Muscle fascicles

Muscle fibers Troponin

T I
Myofebriles C

Myofilaments
• Thin myofilament (actin)
• Thick myofilament (myocine)
• Regulatory proteins (troponin and tropomyocine)
Structure of skeletal muscles
 Fine structure of the skeletal muscle
• Cell membrane is sarcolemma
• Cytoplasm is sarcoplasm
Contains myoglobin, glycogen,
creatin-PK
• sER is sarcoplasmic reticulum.
• A muscle cell has two tubular
structures:
a. Transverse tubules (T-tubules)
Function: conduction of depolariz.
b. Longitudinal tubules (sER)
Function: Ca 2+ storage
 Structure of skeletal muscles

• Muscle fiber cell membrane

is known as sarcolemma
• Muscle fiber cytoplasm is
known as sarcoplasm
• Sarcolemma has
invaginations that
penetrate through the cell
called transverse tubules
or T tubules.
• Sarcoplasm has lots of
mitochondria, lots of
glycogen granules (to
provide glucose for
energy needs) as well as
myofibrils and
sarcoplasmic reticulum.
 Myofibrils
• Each myofibril is made up 1000’s of repeating individual units
known as sarcomeres (pictured below)
• Each sarcomere is an ordered arrangement of thick and thin
filaments. Notice that it has:
– regions of thin filaments by themselves (pinkish fibers)
– a region of thick filaments by themselves (purple fibers)
– regions of thick filaments and thin filaments overlapping.
 Sarcomere
• The sarcomere is flanked by 2 protein structures known as Z
discs.
• The portion of the sarcomere which contains the thick filament
is known as the A band. A stands for anisotropic which is a
fancy way of saying that it appears dark under the microscope.
– The A band contains a zone of overlap (btwn thick & thin
filaments) and an H zone which contains only thick filaments
Muscle Contraction: The Sliding Filament Hypothesis
• Place your right palm on the back of your left hand. Now slide
your right palm toward your left elbow.
– What happened to the distance between your elbows?
• It got shorter!
– This is how muscle contraction occurs.
– The thin filaments slide over the thick filaments. This pulls
the Z discs closer together. When all the sarcomeres in a fiber
do this, the entire fiber gets shorter which pulls on the
endomysium, perimysium, epimysium and attached tendon
and then pulls on the bone. Voila, we have movement.
Sliding Filaments
• All the sarcomeres in a fiber will contract together.
This contracts the fiber itself. The number of fibers
contracting will determine the force of the contraction
of the whole muscle.
• We can actually divide the whole process of muscle
contraction into 4 steps:
– Excitation
– Excitation-contraction coupling
– Contraction
– Relaxation
 Mechanism of muscle contraction
(Excitation-contraction coupling)
When a muscle fibre membrane is depolarized, contraction of the
fibre follows. The process by which depolarization initiates
contraction is called excitation contraction coupling. It has
several steps as follow:
1. Action potential initiated & propagated along the motor nerve
fibre and arrives at the end feet.
2. Opening of VG-Ca-channels and influx of Ca2+ to trigger the
release of Ach.
3. Ach released by Ca-dependent exocytosis and diffuse through
the synaptic cleft and binds to NR on postjunctional membrane.
4. Opening of ligand gated Na-channels and influx of Na+ to
produce EPP.
5. Spread of depolarization through the sarcolemma
6. Spread of depolarization through the T-tubules
 Excitation-contraction coupling
7. Depolarization of T-tubules stimulate SR to release
Ca2+ into sarcoplasm
8. Ca2+ binds to troponin-C
9. Ca2+ and troponin-C combination detaches troponin-I from the
active sites of actin
10. The detachment of troponin-I from actin displaces
tropomyocin, uncovering the active sites of actin filaments.
11. When the active site of actin exposed, the heads of myosin
connect to them, making cross-bridges b/n myosin and actin.
12. The ATPase enzyme on the myosin heads hydrolyze ATP into
ADP + -P plus energy.
13. The released energy causes the movt of the head (power
stroke) towards the centre.
14. The head of myosin is charged with a new molecule of ATP
and then detached from actin leading to relaxation.
 Mechanism of muscle relaxation
It has the following steps
1. Following muscle contraction, Ca2+ is re-uptaken back into SR
by Ca-pump, this requires ATP.
2. Decreased Ca2+ in the sarcoplasm→ Ca2+ detaches from
troponin-C →Tropomyosin covers the active sites of actin.
3. Head of myosin charged with ATP, and detached from actin
Therefore, muscle relaxation is an active process requiring
energy.
• Large amount of energy (ATP) is consumed during muscular
performance for the following activities:
1. To move the head of myosin (power stroke)
2. Active Ca2+ pump from sarcoplasm to SR
3. For Na-K-pump in the membrane
4. For muscle relaxation
Rigor Mortis

• Upon death, muscle cells are unable to prevent calcium

entry. This allows myosin to bind to actin. Since there is
no ATP made postmortem, the myosin cannot unbind and
the body remains in a state of muscular rigidity for almost
the next couple days. This condition is called contracture
 Myasthenia Gravis
• It is the defect in the NMJ, characterized by easy fatigability
of the sk/muscle. Results in progressive weakening of the
skeletal muscles. Why?
• My=muscle, asthen=weakness, gravi=heavy
Possible causes
• Autoimmune disease where antibodies attack the NR on
neuromuscular junctions. High thymopoietin is another
• Decrease in quantity of Ach release
• Decrease in No of NR on neuromuscular junctions
• Decrease in post junctional folds
• Increase in width of synaptic cleft
Treatment:
• Anticholinesterase: anticholinesterases such as neostigmine
or physostigmine. These decrease the activity of acteyl-
cholinesterase.
• Steroids
• Thymoctomy
 Muscle Atrophy and Hypertrophy
Muscle atrophy: Disuse atrophy and
Denervation atrophy
- Denervation atrophy:
Paresis,
Paralysis (UMNL, LMNL)
Muscle hypertrophy: Increase in size of muscle fiber
Changes:
• ↑No of actin and myosin filaments in each fiber
• ↑No of sarcomers
• ↑Enzyme system of glycolysis
• ↑Amount of myoglobin, ↑Mitochondria
• ↑No of capillaries
As a result, there is an increase in the force and strength of
contraction, decrease in fatigability
 Smooth Muscle
• Involuntary, non-striated muscle tissue
• Occurs within almost every organ, forming sheets,
bundles, or sheaths around other tissues.
• Cardiovascular system:
– Smooth muscle in blood vessels regulates blood flow
through vital organs. Smooth muscle also helps
regulate blood pressure.
• Digestive systems:
– Rings of smooth muscle, called sphincters, regulate
movement along internal passageways.
– Smooth muscle lining the passageways alternates
contraction and relaxation to propel matter through the
alimentary canal.
 Smooth Muscle
• Integumentary system:
– Regulates blood flow to the superficial dermis
– Allows for piloerection
• Respiratory system
– Alters the diameter of the airways and changes the resistance to airflow
• Urinary system
– Sphincters regulate the passage of urine
– Smooth muscle contractions move urine into and out of the urinary
bladder
• Reproductive system
– Males
• Allows for movement of sperm along the male reproductive tract.
• Allows for secretion of the non-cellular components of semen
• Allows for erection and ejaculation
– Females
• Assists in the movement of the egg (and of sperm) through the female
reproductive tract
• Plays a large role in childbirth
 Smooth Muscle
• Smooth muscle cells:
– Are smaller: 5-10um in diameter
and 30-200um in length
– Are uninucleate: contain 1 centrally
placed nucleus
– Lack any visible striations
– Lack T-tubules
– Have a scanty sarcoplasmic
reticulum

• Smooth muscle tissue is innervated by the autonomic nervous

system unlike skeletal muscle which is innervated by the
somatic nervous system (over which you have control)
• Only the endomysium is present. Nor perimysium or
epimysium.
 Types of Smooth Muscle

• Smooth muscle varies widely from organ to organ

in terms of:
– Fiber arrangement
– Responsiveness to certain stimuli
• How would the types of integral proteins
that a smooth muscle cell contained
contribute to this?
• Broad types of smooth muscle:
– Single unit (visceral) SM
– Multi unit SM
 Single Unit Smooth Muscle
• More common
• Cells contract as a unit
because they are all connected
by gap junctions - protein
complexes that span the PM’s
of 2 cells allowing the passage
of ions between them, i.e.,
allowing the depolarization of
one to cause the
depolarization of another.
• Some will contract
rhythmically due to
pacemaker cells that have a
spontaneous rate of
depolarization.
 Single Unit Smooth Muscle

• Not directly innervated.

Diffuse release of
neurotransmitters at
varicosities (swellings
along an axon).
• Responsive to variety of
stimuli including stretch
and concentration changes
of various chemicals
• Found in the walls of the
digestive tract, urinary
bladder, and other organs
 Multi-Unit Smooth Muscle
• Innervated in motor units comparable
to those of skeletal muscles
• No gap junctions. Each fiber is
independent of all the others.
• Responsible to neural & hormonal
controls
• No pacemaker cells
• Less common
• Found in large airways to the lungs,
large arteries, arrector pili, internal eye
muscles (e.g., the muscles that cause
dilation of the pupil)
• Why is good to have the digestive
smooth muscle single unit and the
internal eye muscles multi-unit?
Cardiac Muscle
• Striated, involuntary muscle
• Found in walls of the heart
• Consists of branching
chains of stocky muscle
cells. Uni- or binucleate.
• Has sarcomeres & T-tubules
• Cardiac muscle cells are
joined by structures called
intercalated discs – which
consist of desmosomes and
gap junctions. Notice the branching and
– Why do you suppose the intercalated disc,
these are necessary? indicated by the blue arrow.
Autonomic nervous system

51
 Organization of the Nervous System
• 2 big divisions:
1. Central Nervous System
• The brain + the spinal cord
– The center of integration and control
2. Peripheral Nervous System
• The nervous system outside of the brain and
spinal cord
• Consists of:
-31 pairs of spinal nerves
-12 pairs of cranial nerves
• Carry info to and from the spinal cord
• PNS Can be divided further:
– Somatic nervous system
• VOLUNTARY (generally)
• Somatic nerve fibers that conduct impulses
from the CNS to skeletal muscles
– Autonomic nervous system
• INVOLUNTARY (generally)
• Conducts impulses from the CNS to smooth 52
muscle, cardiac muscle, and glands.
 COMPARISON OF Somatic NS VS. ANS
Somatic NS ANS
1. Controls contraction of 1. Controls involuntary activities
the sk/muscle. such as CVS, GIT, sweat
glands
2. Nerve fibres are
originated from the 2. Nerve fibres are originated
anterior horn of the GM from the lateral horn of the
of the spinal cord. GM of spinal cord and CN-III,
VII,IX and X.
3. The motor nerve
3. Autonomic fibres contain two
contains single, long,
neurons
thick and myelinated
axon. 4. There are both cholinergic and
adrenergic fibres acting on
4. The NT is always Ach cholinergic and adrenergic
and the receptor is receptors 53
always NR
Somatic and autonomic neurons

54
Autonomic innervation

55
ANATOMICAL DIVISIONS OF THE ANS

SMG
IMG

56
 Autonomic Nervous System

• Can be divided into:

• Sympathetic
Nervous
System
– “Fight or Flight”
– Parasympathetic
Nervous System
• “Rest and
Digest”

57
Sympathetic Division: (Thoracolumbar out flow)
• Originates in lateral horns of T1-T12 and L1-L2 region of spinal cord            
• Components of the Sympathetic neurons
1. Cell bodies of preganglionic motor neurons are located in the thoracic and
lumbar part of the spinal cord
2. Preganglionic axons synapse in lateral/collateral ganglia, which are
located near the spinal cord far away from the organs being innervated
3. Contains short preganglionic neurons which are cholinergic.
4. Sympathetic postganglionic axons travel from the lateral/collateral ganglia to
the target organ
5. Contains long postganglionic neurons
Function:
• Sympathetic mass discharge during emergency" situations (flight or fight
response)
• Sympathetic mass discharge: simultaneous activation of various organs
• The sympathetic neurons have excitatory effects on almost all body tissues. Their
effect is excitatory the CVS and inhibitory on the GIT.
• Catabolic, increases MR and energy output
• Tonic discharge of impules to the heart and blood vessels 58
Origin of sympathetic motor
neurns

59
 Neuronal organizations of the ANS

Thoraco
lumbar
ACh-N ACh-M

Sweat glands
Bld Vess. Sk/m 60
Certain splanchnic nerves synapse on hormone-producing cells of the adrenal
medulla – the interior of the adrenal glands which sit upon the kidneys.

How does this contribute

to the “diffuseness” of
sympathetic activity?
 ANS Neurotransmitters

Sympathetic NS

62
 ANS Neurotransmitters

• Parasympathetic NS
63
 Parasympathetic Division: (Craniosacral)
• Originates from cranial and sacral regions.
• Cranial components are part of CN III (Oculomotor), VII (Facial), IX
        (Glossopharyngeal), and X (Vagus)
• Sacral components from S2 - S4 segments of the spinal cord

Components of the parasympathetic neurons

1. Cell bodies of preganglionic motor neurons located in parts of certain nuclei of cranial
nerves and in the sacral part of the spinal cord
2. Preganglionic axons synapse in terminal ganglia which are
located close to or on the organ being innervated
3. Contains long preganglionic neurons
4. Parasympathetic postganglionic axons travel from the terminal ganglia to the target
organ
5. Contains short postganglionic cholinergic neurons
Function
• Regulation of digestion, defecation and micturition
• Concervation of energy, anabolic, maintains a homeostatic environment  ”resting and
digesting" system
• No mass discharge, discrete activities
• There is tonic impulse discharge to the heart
• Parasympathetic neurons in general have inhibitory effect on almost all body tissues
except in the GIT. They have excitatory effects on the GIT. 64
 Properties of pre- and post ganglionic neurons
• All preganglionic neurons are cholinergic neurons. They secrete acetylcholine
and are excitatory
• Sympathetic post ganglionic neurons are adrenergic with few exceptions
• They secrete nor epinephrine and are either excitatory or inhibitory.
• Parasympathetic post ganglionic neurons are cholinergic. They secrete
acetylcholine and are either excitatory or inhibitory.
Receptors in the autonomic nervous system
• Two principal receptors of acetylcholoine (Cholinergic receptors)
a. Nicotinic receptors
• b. Muscarinic receptors
• Acetylcholine activates both receptors.
• Muscarinic receptors are found on all effector cells stimulated by
postganglionic cholinergic neurons of PaSN.
• Nicotinic receptors are found between pre- and post ganglionic neurons
(ganglia) of both PaNS and SyNS. Also found at many non- autonomic nerves
e.g., NMJ
Adrenergic receptors
• a. Alpha receptors –subtypes include alpha1 and alpha2
• b. Beta receptors- subtypes include beta1 and beta2 65
Origin of parasympathetic motor
neurons

66
 Autonomic ganglia
• A ganglion (ganglia = pl) is a collection of cell bodies outside the CNS
• A nucleus (nuclei = pl) is a collection of cell bodies within the CNS
Types of the autonomic ganglia
1. Lateral (paravertibral) ganglia
• Are sympathetic ganglia
• Form sympathetic chains on both sides of the vertebral column
2. Collateral (prevertebral) ganglia
• Are also sympathetic ganglia
• Located in midway b/n the cord and the viscera
• 3 types: celiac g., superior mesentric g. and Inferior MG
3. Terminal ganglia: a parasympathetic ganglia, located near/within the organ
that they innervate
Function of the autonomic ganglia
1. Relay stations
2. Expansion centers
67
3. Distribution centers
 Acetylcholine Synthesis
choline
acetyltransferase

Choline + Acetyl CoA ACh + CoA

68
 Autonomic Receptor
Receptor Name Typical Locations Result of Ligand Binding
Cholino ceptors     
  Muscarinic M1 CNS neurons, sympathetic Formation of IP3 and
  postganglionic neurons DAG, increased
intracellular Ca
  Muscarinic M2 Myocardium, smooth muscle, CNS Opening of K channels,
  neurons inhibition of adenylyl
cyclase
  Muscarinic M3 Exocrine glands, vessels (smooth Like M1 receptor-ligand
  muscle and endothelium); CNS binding
neurons
  Muscarinic M4 CNS neurons; possibly vagal nerve Like M2 receptor-ligand
endings binding
  Muscarinic M5 Vascular endothelium, especially Like M1 receptor-ligand
cerebral vessels; CNS neurons binding
  Nicotinic NN Postganglionic neurons, some Opening of Na+, K+
  presynaptic cholinergic terminals channels, depolarization
69
  Nicotinic NM Skeletal muscle neuromuscular Opening of Na+, K+
 Autonomic Receptor
Receptor Name Typical Locations
Adrenoceptors   
  Alpha1 Postsynaptic effector cells,
  especially smooth muscle of
blood vessels
  Alpha2 Presynaptic adrenergic nerve
  terminals, platelets, lipocytes,
smooth muscle
  Beta1 Postsynaptic effector cells,
  especially heart, lipocytes, brain
  Beta2 Postsynaptic effector cells,
  especially smooth muscle of
bronchi and cardiac muscle
  Beta3 Postsynaptic effector cells,
  especially lipocytes; heart
Result of Ligand Binding
 
Formation of IP3 and DAG,
increased intracellular
calcium
Inhibition of adenylyl
cyclase, decreased cAMP
Stimulation of adenylyl
cyclase, increased cAMP
Stimulation of adenylyl
cyclase and increased
cAMP.  
Stimulation of adenylyl
cyclase and increased
cAMP1 70
 Choline +

ACh Acetyl-COA

ACh

Botulinum toxin A AChE

N
curare M
atropine
AChE
71
 Norepinephrine Synthesis

tyrosine DOPA dopamine

hydroxylase decarboxylase b hydroxylase

Tyrosine DOPA DA NE

72
Monoamines

MAO
Reserpine

A
COMT
β1, 2,
α1
MAO
73
 Autonomic reflexes
• A reflex is a fast and involuntary action inresponse to a stimulus
• A reflex action consists of an action that is signaled to CNS and a reaction
ordered by the CNS
• Any reflex is transmitted through a reflex arc
• A reflex arc of any reflex has 5-components
1. A receptor that detects changes
2. Afferent (sensory) pathway
3. Integrating centre (spinal cord, brain stem, HT, cerebral c.)
4. Efferent (motor) pathway
5. Effectors organs (Cardiac muscles, smooth muscles and secretary glands)
Representative autonomic reflexes
• The Baroreceptor reflex
• The chemoreceptor reflex
• Defecation reflex
• Micturition reflex
74
 Effects of ANS on various organs
Effect of Sympathetic Effect of Parasympathetic
Organ Stimulation Stimulation
Eye
  Pupil: Iris radial muscles (α1-AR) Contraction leads to pupillary None
Dilation (mydriasis) Contraction leads to pupillary
None constricted (miosis)
Pupil: Iris circular muscles (M-R)
  Ciliary muscle Slight relaxation (far vision) Constricted (near vision)
Glands Vasoconstriction and slight Stimulation of copious
secretion secretion
  Nasal + ++
  Lacrimal + ++
  Salivary glands + ++
   GIT glands Inhibited +++
Pancreatic secretions Inhibited Increased
Sweat glands Copious sweating (cholinergic) Sweating on palms of hands
Apocrine glands Thick, odoriferous secretion None
Systemic Blood vessels Most often constricted 75
Most often little or no effect
 Effects of ANS on various organs
Effect of Sympathetic Effect of Parasympathetic
Organ Stimulation Stimulation
Heart Enhances all activities Inhibits all activites
  Muscle +ve Chronotropic effect Slowed rate
  (↑ HR)

+ Inotropic effect Decreased force of

(↑ Force of contraction) contraction (esp. of atria)

  Coronary vessels Vasodilation (β2) Vasoconstriction

Lungs
  Bronchi Broncho-dilation (β2) Brocho-constricted
  Blood vessels Mildly constricted ? Dilated
Gut Inhibits all activities Enhances all activities
  Lumen Decreased peristalsis and Increased peristalsis and
tone tone
  Sphincter Increased tone (most times) Relaxed (most times) 76
 Effects of ANS on various organs
Effect of Sympathetic Effect of Parasympathetic
Organ Stimulation Stimulation
Liver ↑Glycogenolysis Slight glycogen synthesis
↑Glucose released
Gallbladder and bile ducts Relaxed Contracted
Kidney Vasoconstriction None
↓RBF = ↓UO and ↑renin
secretion
Bladder
  Detrusor Relaxed (slight) Contracted
  Trigone Contracted Relaxed
Penis Ejaculation Erection
Systemic arterioles
  Abdominal viscera Constricted None
  Muscle Constricted (adrenergic α) None
  Dilated (adrenergic β2)  
 
Dilated (cholinergic)   77
 Effects of ANS on various organs
Effect of Sympathetic Effect of Parasympathetic
Organ Stimulation Stimulation
Blood

  Coagulation Increased None

  Glucose Increased None

  Lipids Increased None

Basal metabolism Increased up to 100% None

Adrenal medullary secretion Increased None

Mental activity Increased None

Piloerector muscles Contracted None

Skeletal muscle Increased glycogenolysis None

 
Increased strength  None

Fat cells Lipolysis None 78

 How Does the Brain Control the
ANS?
• The hypothalamus is the Boss:
– Its anterior and medial regions direct parasympathetic
function while its posterior and lateral regions direct
sympathetic function
– These centers exert control directly and via nuclei in
the reticular formation (e.g., the cardiovascular centers
in the MO, respiratory centers in MO and pons, etc.)
– The connection of the limbic system to the
hypothalamus mediates our “flight or flight” response
to emotional situations.
– The relationship btwn the hypothalamus and the
amygdala and periaquaductal gray matter allow us to
respond to fear.
 Pharmacology of the ANS
• Several drugs act in the body by modulating
sympathetic and parasympathetic nerves.

Sympathomimetic

• Drugs that act on adrenergic effectors organs are called

drugs.
• These drugs have sympathetic- like effects.

– Epinephrine
– Nor epinephrine
– Methoxamine
81
 Sympathomimtics
• Drugs that stimulate specific adrenergic receptors but not
others include:
» Phenylephrine
» Isoprotrenol
» Albuferol
• Drugs that cause release of catcholamines from the nerve
endings (indirect sympathomimetics). Release of NE yields
sympathetic effects.
» Ephedrine
» Tyramine
» Amphetamine
» Cathinon/cathin 82
 Pharmacology of the ANS
Drugs that block adrenergic activity are:
1. Synthesis and storage of NE can be prevented by:
– Reserpine
2. Release of NE can be blocked by
– Guanethidine
3. Alpha receptors can be blocked by:
– Phenoxybenzamine
– Phentolamine
4. Drugs blocking beta1 and beta2 receptors
– Propranolol
– Metoprolol
5. Drugs that block nerve impulse transmission through
autonomic ganglia of both PaSN and SyNS
– Hexamthonium 83
 Pharmacology of the ANS
• Parasympathomimetic Drugs
– Pilocarpine
– Methacholine
– Acetylcholine
– Bethanechol
– Carbachol
• Drugs having a parasympathetic potentiating effect
Anticholentrase drugs
– Neostegmine
– Physostigmine
– Ambenonium
– Malathion
84
– DFP
 Cholinergic Antagonists
Receptor blockers
A. Nicotinic receptor blockers: competetive NM blockers.
They compete with Ach for NR
Curare alkaloids (d-tubocurarine)
Succinylcholine (Saxamethonium)
Alcuronium (alloferin)
Decamethonium
α-cobratoxin
Palcuronium (Povalin)
Gallamine (Flaxedile)
B. Muscarinic receptor blockers - Atropine
- Homatropin
- Scopolamine
• Ach-release inhibitors
Botulinum Toxin 85
Black Widow Spider Venom ~