1
9. Muscular System:
Histology and Physiology
Prepared by: Mirza Anwar Baig
M.Pharm (Pharmacology)
Anjuman I Islam's Kalsekar Technical Campus,
School of Pharmacy.
New Panvel,Navi Mumbai
1
2
Contents
:
1.
Cardiac muscles
2.
Smooth muscles
3.
Skeletal muscles
4.
Neuromuscular transmission and contraction
of skeletal muscle
5.Energy metabolism in the muscle
6.Types of muscle contractions
7.Muscle tone
3
Functions of Muscular System
1.
Body movement (Locomotion)
2.
Maintenance of posture
3.
Respiration
Diaphragm and intercostal contractions
4.
Communication (Verbal and Facial)
5.
Constriction of organs and vessels
1.
Peristalsis of intestinal tract
2.
Vasoconstriction of b.v. and other structures (pupils)
6.
Heart beat
7.
Production of body heat (Thermogenesis)
3
4
Properties of Muscle
1.
Excitability:
capacity of muscle to respond
to a stimulus
2.
Contractility:
ability of a muscle to shorten
and generate pulling force
3.
Extensibility:
muscle can be stretched back
to its original length
4.
Elasticity:
ability of muscle to recoil to
original resting length after stretched
4
5
Types of Muscle
•
Skeletal
–
Attached to bones
–
Makes up 40% of body weight
–
Responsible for locomotion, facial expressions, posture,
respiratory movements, other types of body movement
–
Voluntary in action; controlled by somatic motor neurons
•
Smooth
–
In the walls of hollow organs, blood vessels, eye, glands,
uterus, skin
–
Some functions: propel urine, mix food in digestive tract,
dilating/constricting pupils, regulating blood flow,
–
Controlled involuntarily by endocrine and autonomic nervous
systems
•
Cardiac
–
Heart: major source of movement of blood
–
Autorhythmic
–
Controlled involuntarily by endocrine and autonomic nervous
systems
5
6
Connective Tissue Sheaths
•
Connective Tissue of a Muscle
–
Epimysium
. Dense regular, surrounding entire muscle
•
Separates muscle from surrounding tissues and organs
•
Connected to the deep fascia
–
Perimysium
. Collagen and elastic fibers surrounding a
group of muscle fibers called a
fascicle
•
Contains b.v and nerves
–
Endomysium
. Loose connective tissue that surrounds
individual
muscle fibers
•
Also contains b.v., nerves, and satellite cells
(embryonic stem cells function in repair of muscle
tissue
•
Collagen fibers of all 3 layers come together at each end
of muscle to form a
tendon
or
aponeurosis.
6
77
8
Nerve
and
Blood
Vessel
Supply
•
Motor neurons
–
stimulate muscle fibers to contract
–
Neuron axons branch so that each
muscle fiber
(muscle cell) is innervated
–
Form a neuromuscular junction (= myoneural
junction)
•
Capillary beds surround muscle fibers
–
Muscles require large amts of energy
–
Extensive vascular network delivers necessary
oxygen and nutrients and carries away
metabolic waste produced by muscle fibers
8
9
Basic Features of a Skeletal Muscle
•
Muscle attachments
–
Most skeletal muscles
run from one bone to
another
–
One bone will move
–
other bone remains
fixed
•
Origin
–
less
movable attach-
ment
•
Insertion
–
more
movable attach-
ment
9
10
Skeletal Muscle Structure
•
Composed of muscle cells
(fibers), connective tissue,
blood vessels, nerves
•
Fibers are long, cylindrical,
and multinucleated
•
Tend to be smaller diameter
in small muscles and larger in
large muscles. 1 mm to 4 cm
in length
•
Develop from myoblasts;
numbers remain constant
•
Striated appearance
•
Nuclei are peripherally located
10
(cytoplasm of fiber)
•
Contains many of the same organelles seen in other cells
•
An abundance of the oxygen-binding protein
myoglobin
–
Punctuated by openings called the
transverse tubules (T-
tubules)
•
Narrow tubes that extend into the sarcoplasm at right
angles to the surface
•
Filled with extracellular fluid
•
Myofibrils
-cylindrical structures within muscle fiber
–
Are bundles of protein filaments (=
myofilaments
)
•
Two types of myofilaments
1.
Actin filaments (thin filaments)
2.
Myosin filaments (thick filaments)
–
At each end of the fiber, myofibrils are anchored to the inner
surface of the sarcolemma
–
When myofibril shortens, muscle shortens (contracts)
11
12
Sarcoplasmic Reticulum (SR)
•
SR is fluid-filled system of membranous sacs
–
runs longitudinally and surrounds each myofibril
–
Form chambers called
terminal cisternae
on
either side of the T-tubules
•
A single T-tubule and the 2 terminal
cisternae form a
triad
•
SR stores Ca
++
when muscle not contracting
–
When stimulated, calcium released into
sarcoplasm
–
SR membrane has Ca
++
pumps that function to
pump Ca
++
out of the sarcoplasm back into the
SR after contraction
12
13
Sarcoplasmic
Reticulum
(
SR
)
Figure 9.5
13
14
Parts of a Muscle
14
15
Sarcomeres
:
Z
Disk
to
Z
Disk
•
Sarcomere
repeating
functional
units
of
a
myofibril
–
About
10,000
sarcomeres
per
myofibril
,
end
to
end
–
Each
is
about
2
µ
m
long
•
Differences
in
size
,
density
,
and
distribution
of
thick
and
thin
filaments
gives
the
muscle
fiber
a
banded
or
striated
appearance
.
–
A
bands
:
a
dark
band
;
full
length
of
thick
(
myosin
)
filament
–
M
line
:
protein
to
which
myosins
attach
–
H
zone
:
thick
but
NO
thin
filaments
–
I
bands
:
a
light
band
;
from
Z
disks
to
ends
of
thick
filaments
•
Thin
but
NO
thick
filaments
•
Extends
from
A
band
of
one
sarcomere
to
A
band
of
the
next
sarcomere
–
Z
disk
:
filamentous
network
of
protein
.
Serves
as
attachment
for
actin
myofilaments
–
Titin
filaments
:
elastic
chains
of
amino
acids
;
keep
thick
and
thin
filaments
in
proper
alignment
15
16
Structure of Actin and Myosin
16
17
Myosin (Thick) Myofilament
•
Many elongated myosin molecules
shaped like golf
clubs
.
•
Single
filament contains roughly
300 myosin
molecules
•
Molecule consists of two heavy myosin molecules
wound together to form a rod portion lying parallel to
the myosin myofilament and two heads that extend
laterally.
Myosin heads:
•
Can bind to active sites on the actin molecules to form
cross-bridges. (
Actin binding site
)
•
Attached to the rod portion by a hinge region that can
bend and straighten during contraction.
•
Have ATPase activity:
activity that breaks down
adenosine triphosphate (ATP), releasing energy.
•
Part of the
energy is used to bend the hinge region
of
the myosin molecule during contraction.
18
Structure
and
Arrangement
of
Myosin
Molecules
Within
Thick
Filament
18
19
Actin (Thin)
Myofilaments
•
Thin
Filament
:
composed
of
3
major
proteins
1.
F
(
fibrous
)
actin
2.
Tropomyosin
3.
Troponin
•
Two
strands
of
fibrous
(
F
)
actin
form
a
double
helix
extending
the
length
of
the
myofilament
;
attached
at
either
end
at
sarcomere
.
–
Composed
of
G
actin
monomers
each
of
which
has
a
myosin
-
binding
site
(
see
yellow
dot
)
–
Actin
site
can
bind
myosin
during
muscle
contraction
.
•
Tropomyosin
:
an
elongated
protein
winds
along
the
groove
of
the
F
actin
double
helix
.
•
Troponin
is
composed
of
three
subunits
:
–
Tn
/
A
:
binds
to
actin
–
Tn
/
T
:
binds
to
tropomyosin
,
–
Tn
/
C
:
binds
to
calcium
ions
.
19
20
Role
of
Calcium
in
Cross
-
Bridge
Formation
•
During
relaxed
state
20
21
Role
of
Calcium
in
Cross
-
Bridge
Formation
•
Excited
21
2222
2323
24CROSS-BRIDGE CYCLE
24
25
Changes in Banding Pattern During Shortening
25
26
Sliding Filament Mechanism
Cross
bridge
interaction
between
actin
and
myosin
brings
about
muscle
contraction
by
means
of
the
sliding
filament
mechanism
.
26
27
Sliding Filament Mechanism
•
Increase
in
Ca
2+
starts
filament
sliding
•
Decrease
in
Ca
2+
turns
off
sliding
process
•
Thin
filaments
on
each
side
of
sarcomere
slide
inward
over
stationary
thick
filaments
toward
center
of
A
band
during
contraction
•
As
thin
filaments
slide
inward
,
they
pull
Z
lines
closer
together
•
Sarcomere
shortens
27
28
Sliding Filament Mechanism
•
All
sarcomeres
throughout
muscle
fiber
’
s
length
shorten
simultaneously
•
Contraction
is
accomplished
by
thin
filaments
from
opposite
sides
of
each
sarcomere
sliding
closer
together
between
thick
filaments
.
28
29
Power
Stroke
•
Activated
cross
bridge
bends
toward
center
of
thick
filament
,
“
rowing
”
in
thin
filament
to
which
it
is
attached
–
Sarcoplasmic
reticulum
releases
Ca
2+
–
Myosin
heads
bind
to
actin
–
Hydrolysis
of
ATP
transfers
energy
to
myosin
head
and
reorients
it
–
Myosin
heads
swivel
toward
center
of
sarcomere
(
power
stroke
)
–
ATP
binds
to
myosin
head
and
detaches
it
from
actin
29
30
Contraction
-
Relaxation
Steps
Requiring
ATP
•
Splitting
of
ATP
by
myosin
ATPase
provides
energy
for
power
stroke
of
cross
bridge
•
Binding
of
fresh
molecule
of
ATP
to
myosin
lets
bridge
detach
from
actin
filament
at
end
of
power
stroke
so
cycle
can
be
repeated
•
Active
transport
of
Ca
2+
back
into
sarcoplasmic
reticulum
during
relaxation
depends
on
energy
derived
from
breakdown
of
ATP
30
31
Neuromuscular
Junction
•
Region
where
the
motor
neuron
stimulates
the
muscle
fiber
•
The
neuromuscular
junction
is
formed
by
:
1.
End
of
motor
neuron
axon
(
axon
terminal
)
•
Terminals
have
small
membranous
sacs
(
synaptic
vesicles
)
that
contain
the
neurotransmitter
acetylcholine
(
ACh
)
2.
The
motor
end
plate
of
a
muscle
•
A
specific
part
of
the
sarcolemma
that
contains
ACh
receptors
•
Though
exceedingly
close
,
axonal
ends
and
muscle
fibers
are
always
separated
by
a
space
called
the
synaptic
cleft
31
32
Motor
Unit
:
The
Nerve
/
Muscle
Functional
Unit
Figure 9.12
(a)
32
33
Motor
Unit
:
The
Nerve
/
Muscle
Functional
Unit
•
A
motor
unit
is
a
motor
neuron
and
all
the
muscle
fibers
it
supplies
•
The
number
of
muscle
fibers
per
motor
unit
can
vary
from
a
few
(4
_
6)
to
hundreds
(1200
_
1500)
•
Muscles
that
control
fine
movements
(
fingers
,
eyes
)
have
small
motor
units
•
Large
weight
/
bearing
muscles
(
thighs
,
hips
)
have
large
motor
units
33
34
Motor Unit: The Nerve-Muscle
Functional Unit contd...
•
Muscle
fibers
from
a
motor
unit
are
spread
throughout
the
muscle
–
Not
confined
to
one
fascicle
•
T
herefore
,
contraction
of
a
single
motor
unit
causes
weak
contraction
of
the
entire
muscle
•
Stronger
and
stronger
contractions
of
a
muscle
require
more
and
more
motor
units
being
stimulated
(
recruited
)
34
35
Neuromuscular
Junction
Figure 9.7 (a-
c)
35
3636
37
Generation of action potential
37
38
Muscle
contraction
38
3939
40
Major
Events
in
Neuromuscular
Transmission
•
Motor
neuron
depolarization
causes
action
potential
to
travel
down
the
nerve
fiber
to
the
neuromuscular
junction
(1).
•
Depolarization
of
the
axon
terminal
causes
an
influx
of
Ca
2+
(2)
which
triggers
fusion
of
the
synaptic
vesicles
(3)
and
release
of
neurotransmitter
(
Acetylcholine
;
ACh
) (4).
•
ACh
diffuses
across
the
synaptic
cleft
and
binds
to
post
/
synaptic
ACh
receptor
(
AChR
)
located
on
the
muscle
fiber
at
the
motor
end
/
plate
(5).
•
Binding
of
ACh
to
AChRs
opens
the
channels
causing
an
influx
of
Na
(5),
depolarization
of
the
sarcolemma
that
travels
down
the
t
/
tubules
(6)
and
ultimately
causes
the
release
of
Ca
2+
from
the
sarcoplasmic
reticulum
/
CONTRACTION
.
•
Unbound
ACh
in
synaptic
cleft
defuses
away
or
is
hydrolyzed
(
inactivated
)
by
acetylcholinesterase
(
AChE
)
(7).
40
41
Muscle Response to Strong Stimuli
•
Muscle force depends
upon the
number
of
fibers stimulated
–
More fibers contracting
results in greater muscle
tension
•
Muscles can continue to
contract unless they run
out of energy
41
42
How Do Muscles Get Energy?
•
Initially
,
muscles
use
stored
ATP
for
energy
–
ATP
bonds
are
broken
to
release
energy
–
Only
4
–
6
seconds
worth
of
ATP
is
stored
by
muscles
•
After
this
initial
time
,
other
pathways
must
be
utilized
to
produce
ATP
42
43
Skeletal
muscle
energy
metabolism
43
44
1. Creatine Phosphate (high-energy molecule)
•
Muscle cells store CP
•
CP transfers energy to ADP, to
regenerate ATP by direct
phosphorylation of ADP
•
Creatine synthesize in
liver,pancrease,kidneys
•
The
enzyme creatine kinase
forms CP from creatine and
ADP
44
45
2.Anaerobic Respiration
•
Anaerobic glycolysis and
lactic acid formation
–
Reaction that breaks
down glucose without
oxygen
–
Glucose is broken down
to pyruvic acid to
produce some ATP
–
Pyruvic acid is converted
to lactic acid
•
This reaction is not as
efficient, but is fast
–
Huge amounts of glucose
are needed
–
Lactic acid produces
muscle fatigue
45
46
3.Aerobic Respiration
•
Glucose is broken
down to carbon
dioxide and water,
releasing energy (ATP)
•
This is a
slower
reaction that requires
continuous oxygen
•
A series of metabolic
pathways occur in the
mitochondria
46
47
Muscle Fatigue & Oxygen Debt
•
When a muscle is fatigued, it is
unable to contract even with a
stimulus
•
Common cause for muscle
fatigue is
oxygen debt
–
Oxygen must be
“
repaid
”
to
tissue to remove oxygen
deficit
–
Oxygen is required to get rid
of accumulated lactic acid
•
Increasing acidity (from lactic
acid) and lack of ATP causes
the muscle to contract less
47
48
48
Smooth
Muscle
•
Located in
the blood vessels, the
respiratory tract, the iris of the eye,
the gastro-intestinal tract
•
The contractions are slow and
uniform
•
Functions
to alter the activity
of
various body parts to meet the needs
of the body at that time
•
Is fatigue resistant
•
Activation is
involuntary
49
Smooth
Muscle
•
Cells are not striated
•
Fibers smaller than those
in skeletal muscle
•
Spindle-shaped; single,
central nucleus
•
More actin than myosin
•
No sarcomeres
–
Not arranged as
symmetrically as in
skeletal muscle, thus NO
striations.
•
Dense bodies instead of Z
disks
–
Have
noncontractile
intermediate filaments
49
50
Smooth
Muscle
Figure 9.24
•
Grouped into sheets in walls of hollow organs
•
Longitudinal layer
–
muscle fibers run parallel to
organ
’
s long axis
•
Circular layer
–
muscle fibers run around
circumference of the organ
•
Both layers participate in peristalsis
50
51
51
Cardiac
Muscle
•
Has characteristics of both skeletal
and smooth muscle
•
Functions to provide the contractile
activity of the heart
•
Contractile activity can be gradated
(like skeletal muscle)
•
Is
very fatigue resistant
•
Activation of cardiac muscle is
involuntary
(like smooth muscle)
52
Cardiac Muscle
•
Found only in heart where it forms a thick layer
called the
myocardium
•
Striated fibers that branch
•
Each cell usually has
one centrally-located nucleus
•
Fibers joined by intercalated disks
–
IDs are composites of
desmosomes
and
gap
junctions
–
Allow excitation in one fiber to spread quickly to
adjoining fibers
•
Under control of the ANS (involuntary) and endocrine
system (hormones)
•
Some cells are
autorhythmic
–
Fibers
spontaneously
contract ( Pacemaker cells)
52
53
Cardiac
Muscle
Tissue
Figure 10.10a
53
54
Cardiac
Muscle
and
Heart
Function
•
Cardiac
muscle
fibers
are
striated
–
sarcomere
is
the
functional
unit
•
Fibers
are
branched
;
connect
to
one
another
at
intercalated
discs
.
The
discs
contain
several
gap
junctions
•
Nuclei
are
centrally
located
•
Abundant
mitochondria
•
SR
is
less
abundant
than
in
skeletal
muscle
,
but
greater
in
density
than
smooth
muscle
•
Sarcolemma
has
specialized
ion
channels
that
skeletal
muscle
does
not
–
voltage
/
gated
Ca
2+
channels
•
Fibers
are
not
anchored
at
ends
;
allows
for
greater
sarcomere
shortening
and
lengthening
54
5555
56
How
are
cardiac
contractions
started
?
Cardiac
conduction
system
•
Specialized
muscle
cells
“
pace
”
the
rest
of
the
heart
;
cells
contain
less
actin
and
myosin
,
are
thin
and
pale
microscopically
•
Sinoatrial
(
SA
)
node
;
pace
of
about
65
bpm
•
Internodal
pathways
connect
SA
node
to
atrioventricular
(
AV
)
node
•
AV
node
could
act
as
a
secondary
pacemaker
;
autorhythmic
at
about
55
bpm
•
Bundle
of
His
•
Left
and
right
bundle
branches
•
Purkinje
fibers
;
also
autorhythmic
at
about
45
bpm
ALL
CONDUCTION
FIBERS
CONNECTED
TO
MUSCLE
FIBERS
THROUGH
GAP
JUNCTIONS
IN
THE
INTERCALATED
DISCS
56
57
Muscle tone:
•
Muscle tone (tonos=tension), a small amount of tautness
or tension in the muscle due to weak, involuntary
contractions of its motor units.
•
Muscle tone keeps skeletal muscles firm, but it does not
result in a force strong enough to produce movement.
For example,
1.
Upright position of head
:
when the muscles in the back of
the neck are in normal tonic contraction, they keep the head
upright and prevent it from slumping forward on the chest.
2.
Gastrointestinal tract:
where the walls of the digestive organs
maintain a steady pressure on their contents.
3.
Walls of blood vessels:
plays a crucial role in maintaining
blood pressure.
58
Disorders of Muscle tone:
•
Hypotonia
refers to decreased or lost muscle tone.
•
Such muscles are said to be
flaccid
.
•
Flaccid muscles are loose and appear flattened rather
than rounded.
•
Certain disorders of the nervous system and disruptions
in the balance of electrolytes (especially sodium,
calcium, and, to a lesser extent, magnesium) may result
in
flaccid paralysis
, which is characterized by loss of
muscle tone, loss or reduction of tendon reflexes, and
atrophy (wasting away) and degeneration of muscles.
59
Hypertonia
refers to increased muscle tone and is
expressed in two ways:
spasticity or rigidity.
1.Spasticity
is characterized by increased muscle tone
(stiffness)
•
Certain disorders of the nervous system and
electrolyte disturbances such as those previously
noted may result in
spastic paralysis, partial
paralysis
in which the muscles exhibit spasticity.
2.
Rigidity
refers to increased muscle tone in which
reflexes are not affected.