Muscle Physiology muscle is important tissue in maintenance of body posture - Copy.ppt

Muscle Physiology
Arba Minch University
College of Medicine & Health Sciences
School of Medicine
Physiology Unit
By:
Tariku A. (Msc in Medical Physiology)

At the end of this chapter, the student will be able to:
1.List the 3 types of muscle.
2.Define characteristics of muscle.
3.Enumerate functions of muscle.
4.Explain the skeletal & smooth muscle types.
5.Compare skeletal, smooth & cardiac muscles.
2
3/18/2024 Tariku A. (Muscle Physiology)

• Introduction
• Function of muscle
• Types of muscle
• Characteristics of muscle
• Skeletal muscle:
– Excitation
– Excitation-contraction coupling
– Contraction
– Relaxation
– Muscle metabolism
– Types of muscle fiber
• Smooth muscle
• Cardiac muscle 3

Introduction
• Muscle is one of our 4 tissue types and combined
with nerves, blood vessels, and various connective
tissues is what makes up those muscle organs that
are familiar to us.
• Muscles are quite complex and are a marvel of both
biology and physics.
4

Muscle Functions
5

Muscle Functions…
6

Muscle Functions…
7

3 Types of Muscle Tissue
8

Characteristics of Muscle Tissue
9

Characteristics of Muscle Tissue…
10

Skeletal Muscle – the organ…
12

Skeletal Muscle Microanatomy
13

14

• Muscle cell version of
smooth ER.
• Functions as a
calcium storage depot
in muscle cells.
• Loose network of this
membrane bound
organelle surrounds
all the myofibrils in a
muscle fiber.
15

16

• 2 -types of myofilaments (thick & thin) make up myofibrils.
• Thick myofilaments are made up of the protein myosin.
A single myosin protein
resembles 2 -golf clubs
whose shafts have been
twisted about one another.
About 300 of these
myosin molecules are
joined together to form a
single thick filament
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Tariku A. (Muscle Physiology)
The myosin head has actin
and ATP binding sites.

Myofilaments…
19

20

Sarcomere…
21

22

23

24

The Sliding Filament Hypothesis…
25

The Sliding Filament Hypothesis…
26

Sliding Filaments…
27

28

Excitation…
29

Excitation…
• Plasma membrane has integral proteins that act as
gated ion channels.
 channels that are normally closed, but in response to a
certain signal, they will open & allow specific ions to pass
through them. They are:
– Ligand-gated  the binding of an extracellular molecule
(hormone, NT) causes these channels to open.
– Voltage-gated  Vm causes these channels to open.
– Mechanically-gated  stretch or mechanical pressure
opens these channels.
• When a channel is open, its specific ion (s) will enter or exit
depending on their electrochemical gradient.
30

Excitation…
31

Excitation…
 Synaptic end bulb is filled
with vesicles that contain a
NT, ACh.
 Minute space between the
synaptic end bulb & the
sarcolemma is known as
the synaptic cleft.
 There is a depression in
the sarcolemma at the
synaptic cleft known as a
motor end-plate, chock full
of ACh receptors.
32

Mechanism of Excitation
1. A nerve signal will arrive at the synaptic end bulb and this
will cause the ACh-containing vesicles to undergo exocytosis.
2. ACh will diffuse across the synaptic cleft & bind to the ACh
receptors. Actually, these receptors are Ligand-gated Na+
channels. The binding of ACh causes them to open.
3. Na+ will rush into
the cell, making
the local cell interior
more positive.
= This is known as
depolarization.
= It is a local event!
33

Mechanism of Excitation…
34

35

• At this point, slow K+ channels have opened & K+ efflux
occurs. This returns Vm back to its resting level. This is r
epolarization.
• If we were to graph this change in Vm over time, it woul
d look somewhat like the animation below.
• This is known as an AP
36

• AP can propagate itself across the surf
ace of the sarcolemma.
– The depolarization caused by the N
a+ influx in one particular area of t
he sarcolemma causes voltage-gat
ed channels in the adjacent membr
ane to open.
– The resulting ionic influx then caus
es voltage-gated channels to open
in the next patch of membrane and
so on and so on.
37

Excitation-Contraction Coupling
1. AP travels along the sarcolemma in both direction
away from the motor end-plate.
2. T-tubules are invaginations of the sarcolemma, the
AP will spread down & through them as well.
38
DHP= dihydropyridine receptor

Excitation-Contraction Coupling…
3. T-tubule contains voltage sensitive protein (arrow)
that change their conformation in response to a
significant Vm.
4. These are physically linked to Ca2+ channels in SR.
– Upon Vm, the voltage sensors change their conformation.
This mechanically opens the Ca2+ channels in the SR.
5. The SR Ca2+ channels are only open briefly, but a
large Ca2+ gradient exists so large amount of Ca2+
enters the sarcoplasm.
3/18/2024

Excitation-Contraction Coupling…
6. Ca2+ interacts with the 2 regulatory proteins.
7. The 2 contractile proteins slide one over the other.
8. The sarcomere shorten (muscle contraction).
40

Contraction
• Tropomyosin obstructs the myosin binding site on
the G-actin subunits.
• Ca2+ binds to the troponin-C.
– This changes the conformation of troponin & w/c changes
the conformation of tropomyosin which also exposes the
myosin binding site on actin.
41

Contraction…
• Once actin-myosin binding site is exposed, myosin will attach on i
t. At this point:
1. Myosin has just hydrolyzed ATP into ADP & Pi – however both mo
lecules are still bound to the myosin.
– the ATP hydrolysis provide the energy for the “cocking” of the
myosin head
2. Once myosin is bound to actin, the myosin head will release the AD
P & Pi which will cause it change conformation.
– This results in the thin filament sliding along the thick filament.
42

Contraction…
3. Myosin then re
mains bound to
actin until it bin
ds to another A
TP.
4. Myosin then hy
drolyzes the ne
w ATP and the
cycle can begin
again.
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43

44

45
Ca++ binds to troponin Tropomyosin exposes actin
Filaments slide
ATP is broken down
New ATP comes, Ca is removed, ready to detach
myosin head binds to actin
& cross-bridge forms

46

Relaxation
• Ca2+ pumps back into the SR.
– They are unable to do this as long as
the receptor is still binding with ACh.
– ACh is released by the motor neuron
as long as it keeps being stimulated.
• Note that ACh does not remain bound to AChR for very long.
– ACh quickly released & either binds again or more likely to
hydrolyzed by the enzyme ACh esterase.
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47

Relaxation…
• When the muscle ceases being
stimulated, the Ca2+ pumps “w
in” & sarcoplasmic [Ca2+] drop
s.
– Ca2+ stops being available f
or troponin & tropomyosin s
hifts back into its inhibitory
position.
• The muscle then returns back
to its original length via the ela
sticity of the connective tissue
elements, plus the contraction
of antagonistic muscles, and gr
avity.
3/18/2024 48
This animation shows another
way to induce muscle relaxation.
Does it make sense?
48

Rigor Mortis
• Upon death, muscle cells una
ble to prevent Ca2+ entry.
– This allows myosin to
bind with actin.
• Since there is no ATP made po
stmortem, the myosin cannot u
nbind & the body remains in a s
tate of muscular rigidity for
almost the next couple of days.
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49

Muscle Metabolism
• The chemical energy release
d by hydrolysis of ATP is n
ecessary for both contraction
& relaxation of muscle.
• Muscles typically store limite
d amounts of ATP.
So resting muscles must
have energy stored in ot
her ways.
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50
ATP

ATP Use in the Resting Muscle Cell
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Working Muscle
• As we begin exercise, immediately use our stored ATP.
• For the next 15 seconds or so, we turn to the
phosphagen system, the energy stored in creatine-
phosphate.
Creatine-P + ADP Creatine Kinase Creatine + ATP
• The ATP is then available to power contraction and
relaxation.
• The phosphagen system dominates in events such as
the 100m rushing movement or lifting weights.
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52

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53

Working Muscle…
• After the phosphagen system is depleted, the muscles must
find another ATP source.
• The process of anaerobic metabolism maintains ATP supply
for about 30-60s.
– Anaerobic means “without air,” and it is the breakdown of
glucose without the presence of oxygen.
• It usually takes little time for the respiratory and CV systems
to catch up with the muscles and supply O2 for aerobic
metabolism.
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54

Anaerobic Metabolism
• Inefficient.
1. Large amount of glucos
e used for a very smal
l ATP returns.
2. Lactic acid is a toxic end
-product whose presenc
e contributes to muscle
fatigue.
• Dominates in sports tha
t require bursts of spee
d & activity
e.g., Basketball.
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55

Aerobic Metabolism
• Occurs when the respiratory & CV systems have
“caught up with” the working muscles.
– prior to this, some aerobic respiration will occur
thanks to the muscle protein (myoglobin) which
binds & stores O2.
• During rest and light to moderate exercise:
– aerobic metabolism contributes 95% of the
necessary ATP.
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56

Aerobic Metabolism…
• It occurs in the mitochon
dria.
• Pyruvic acid from glycolysis
is the primary substrate.
• The cell also utilizes fatty a
cids and amino acids.
• Aerobic respiration typically
yields 36 ATP per glucose.
– Compare this with anaerob
ic metabolism.
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57

3/18/2024 Tariku A. (Muscle Physiology) 58

Muscle Fatigue
• Physiological inability to respond to
a stimulus.
• Temporary inability of an organ/b
ody part (muscle/nerve cell) to resp
ond to a stimulus & function norm
ally after continuous activity/stimula
tion.
• Results primarily from a relative defi
cit of ATP.
3/18/2024 59
59

Oxygen debts
• Refers to the fact that post-exercise breathing rate >>>
resting breathing rate.
• This excess oxygen intake serves many tasks:
1. Replenish the oxygen stored by myoglobin & hemoglobin
2. Convert remaining lactic acid back into glucose
3. Used for aerobic metabolism to make ATP which is used to:
– Replenish the phosphagen system & glycogen stores
– Power the Na+/K+ pump so as to restore resting ionic
conditions within the cell.
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60

Whole Muscle Contraction
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61

3/18/2024 62
Whole Muscle Contraction…
62

Phases of the Muscle Twitch
1. Latent Period
• Time between stimulus & generation of
tension.
• Includes all time required for:
– excitation
– excitation-contraction coupling and
– stretching of the series elastic components.
2. Contraction
3. Relaxation
3/18/2024 63
63

Motor Units
• Somatic motor neuron & all the skeletal muscle fib
ers it innervates is known as a Motor Unit.
• When this neuron is stimulated, all the muscle fibers it sy
napses upon will be stimulated & contract as a unit.
• The number of muscle fibers per motor unit may be as hi
gh as several 100 or as few as 4.
• The smaller the motor unit, the finer & more delicate th
e movement.
Extraocular muscles typically have small motor units whil
e the large postural muscles have large motor units.
3/18/2024 64
Tariku A. (Muscle Physiology)

Motor Units…
Notice that the muscle fibers of a single unit are not clustered
together but are spread out. What’s the advantage to this ???.
65

Internal vs. External Tension
3/18/2024 Harmegido! 66
 The SEC behaves like fat rubber bands. They stretch easily at first,
but as they elongate they become stiffer and more effective at
transferring the external tension to the resistance.
 Attach a rubber band to a weight & then try to pick it up. What
happens?
66

Resistance & Speed of Contraction
• There is an inverse r/ship b/n
amount of resistance and th
e speed of contraction.
• The heavier the load, the longe
r it takes for the movement to
begin because:
1. Muscle tension, which increases
gradually, must exceed the resis
tance before shortening can occ
ur.
2. More cross-bridges must be for
med, more fibers involved.
3/18/2024 67
67

Types of Muscle Contractions
 Muscle contraction is said to be isometric when th
e muscle does not shorten during contraction.
 Isotonic when it does shorten but the tension
on the muscle remains constant throughout the
contraction.
 Contractions can be:
1. Isometric (iso = same, meter = measure)
2. Isotonic (iso = same, ton = tension)
3/18/2024 68
68

Isotonic Contraction
• Tension reaches a plateau & then the muscle shortens.
3/18/2024 69
69

Isometric Contractions
• The muscle as a whole does not change length and the
tension produced never exceeds the resistance.
3/18/2024 70
70

Types of Skeletal Muscle Fibers
3/18/2024 71
Two main types:
1. Fast fibers
2. Slow fibers
71

Fast vs. Slow Muscle Fibers
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72

Fast Fibers
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73

Fast Fibers…
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74

Fast Fibers…
3/18/2024 75
75

Slow Fibers
(1) Smaller fibers.
(2) Also innervated by smaller nerve fibers.
(3) Highly vascularized
– to supply extra amount of nutrient & oxygen.
(4) Many mitochondria,
– to support high levels of oxidative metabolism.
(5) Large amount of myoglobin, an iron containing
protein similar to Hb in RBCs.
3/18/2024 76
76

Slow Fibers…
Myoglobin:
– combines with oxygen & stores it until needed;
this also greatly speeds oxygen transport to the
mitochondria.
– gives reddish appearance and the name red
muscle.
– A deficit of red myoglobin in fast muscle gives it
the name white muscle.
3/18/2024 77
77

Slow Fibers…
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78

Slow Fibers…
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79

3/18/2024 80
Fast & Slow Muscle Fibers
80

Summary

Other Important Terms
1. Flaccid paralysis
– Weakness or loss of muscle tone typically due to injury
or disease of motor neurons.
2. Spastic paralysis
– Sustained involuntary contraction of muscle (s) with
associated loss of function.
• How do flaccid & spastic paralysis differ?
3. Spasm
– A sudden, involuntary smooth/skeletal muscle twitch.
– Can be painful. Often caused by chemical imbalances.
3/18/2024 82
82

Other Important Terms…
4. Cramp
– A prolonged spasm that causes the muscle to become
stretched & painful.
5. Fibrosis
– Replacement of normal tissue with heavy fibrous
connective tissue (scar tissue).
• How would fibrosis of skeletal muscles affect muscular
strength?
• How would it affect muscle flexibility?
3/18/2024 83
83

Other Important Terms…
6. Hypertrophy
– Increase in size of a cell, tissue or an organ.
• In muscles, hypertrophy of the organ is always due to
cellular hypertrophy (increase in cell size) rather than
cellular hyperplasia (increase in cell number).
• Muscle hypertrophy occurs due to the synthesis of
more myofibrils & glycolytic enzymes.
7. Atrophy
– Reduction in size of a cell, tissue, or organ
• In muscles, it is often caused by disuse.
3/18/2024 84
84

3/18/2024 85
Smooth
Muscle
85

Smooth Muscle
 Involuntary, non-striated
muscle tissue
• Smaller: 1-5µm in diam
& 20-500µm in length.
• Uninucleate: contain
1 centrally placed nucleus
.
• Lack any visible striatio
ns.
3/18/2024 86
86

Smooth Muscle…
3/18/2024 87
87

1. CV system:
 Smooth muscle in blood vessels regulates blood
flow through vital organs, also helps regulate BP.
2. Digestive systems:
 Rings of smooth muscle (sphincters) regulate
movement along internal passageways.
 Smooth muscle lining the passageways alternates
contraction & relaxation to propel matter
through the alimentary canal.
Smooth Muscle location…
88

3. Integumentary system:
– Regulates blood flow to the superficial dermis.
– Allows for piloerection.
4. Respiratory system:
– Alters the diameter of the airways &
changes the resistance to airflow.
5. Urinary system
– Sphincters regulate the passage of urine.
– Smooth muscle contractions move urine into and
out of the urinary bladder.
3/18/2024 89
89

6. Reproductive system
Females
– Assists in the movement of the egg (& of sperm)
through the female reproductive tract.
– Plays a large role in childbirth.
Males
– Allows for:
• movement of sperm along the male
reproductive tract.
• erection & ejaculation.
3/18/2024 90
90

• No Z discs, instead thin filaments are attached to protein st
ructures (dense bodies) which attach to the sarcolemma.
Physical structure of smooth muscle

Smooth Muscle Contraction
• Begins with opening of membrane channels:
– ligand-gated (NTs, hormones, metabolites).
– voltage-gated, or mechanically-gated (stretch).
• Channels allow significant entry of Ca2+ from the ECF.
– Remember smooth muscle has little SR.
• Ca2+ binds to calmodulin & activates it.
– Activated calmodulin activates an enzyme called Myosi
n Light Chain Kinase (MLCK).
3/18/2024 92
92

Smooth Muscle Contraction…
• Activated MLCK will add a ph
osphate group to the myosi
n.
• This enables the myosin to i
nteract with actin.
– Tropomyosin is present,
but not blocking actin’s
myosin binding sites
– Troponin is not present
• Contraction then ensues.
3/18/2024 93
93

3/18/2024 94
Smooth Muscle Relaxation
94

Role of the Smooth Muscle SR
• SR lie near the cell membrane
in some larger smooth muscle
cells.
• Small invaginations of the cell
membrane (caveolae) adjace
nt to the surfaces of these tub
ules.
– Caveolae suggest a rudimentary
analogy of the T tubule of skel
etal muscle.
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95

Role of the Smooth Muscle SR…
• When an AP is transmitted into the caveolae, this
believed to excite Ca2+ release from the adjacent
sarcoplasmic tubules.
– in the same way that APs in skeletal muscle
T tubules cause release of Ca2+ ions from the
skeletal muscle longitudinal sarcoplasmic tubules.
• In general;
– the more extensive the SR in smooth muscle fiber,
the more rapidly it contracts.
3/18/2024 96
96

• Figure: shows comparison of the role of calcium in bringing about
contraction in smooth muscle & skeletal muscle.

Types of Smooth Muscle
 Smooth muscle varies widely fro
m organ to organ in terms of:
1. Physical dimensions
2. Fiber arrangement
- organization into bundles
or sheets
3. Responsiveness to certain stim
uli
4. Characteristics of innervation
5. Function
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98

Multi-Unit Smooth Muscle
• No gap junctions.
– Each fiber are independent of
the others.
• Responsible to neural & ho
rmonal controls
• No pacemaker cells
• Less common
• Found in:
– large airways to the lungs
– large arteries
– eye
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99

Single Unit Smooth Muscle
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100

Single Unit Smooth Muscle…
• Some will contract rhythmically due to pacemaker cells
w/c have a spontaneous rate of depolarization.
• Not directly innervated.
 diffuse release of NTs at varicosities
(swellings along an axon).
• Responsive to variety of stimuli including stretch &
various chemicals.
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101

3/18/2024 102
Cardiac Muscle
102

Cardiac Muscle
• Striated, involuntary mu
scle
• Found in walls of the heart
• Consists of branching chains
of stocky muscle cells.
• Uni or binucleate.
• Has sarcomeres &
T-tubules
• Cardiac muscle cells joined b
y a structure called intercal
ated discs – which consist
of desmosomes & gap juncti
ons.
3/18/2024 103
Notice the branching & the intercalated
disc, indicated by the blue arrow.
103

 Figure: shows AP in contractile
cardiac muscle cells.
• The AP in cardiac contractile cells
differs considerably from the AP
in cardiac autorhythmic cells.

 Excitation–contraction coupling in cardiac
contractile cells

• Figure: shows the relationship of an AP & the refractory period to the
duration of the contractile response in cardiac muscle

Comparison of 3 -Muscle Types

111

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