Muscle Physiology

For Medicine-II Students

BY ;
Mengistu Diress (MSc)
and
Yonas Akalu(MSc)

University of Gondar
CMHS

Department of
Human Physiology
1
 Objectives
At the end of this lesson, students are expected to:

1. Define characteristics of muscle.

2. Enumerate functions of muscle.

3. List and compare the 3 types of muscle cells.

4. Describe physiologic anatomy of skeletal muscle cells

5. Discuss on contraction and relaxation processes of Skeletal

and Smooth muscles

6. Identify disorders related to skeletal muscle cell

dysfunctions. 2
 Outlines
• Introduction.

• Function of muscle.

• Types of muscle.

• Characteristics of muscle.

• Skeletal muscle:

– excitation, excitation contraction coupling, contraction,

relaxation.

• Smooth muscle.

• Cardiac muscle. 3
 Introduction
• 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 movement that enable us to
– produce speech and manipulate objects around us.
• Composed of:
– Skeletal muscle (40% of BW in men and 32% in women)
– Smooth and cardiac muscle (10% of BW)
• Excited chemically, electrically, and mechanically.
4
• Respond to stimuli by activating a contractile mechanism
 Characteristics of Muscle Tissue

1. Excitability: the ability to receive and respond to a stimulus

– Stimulus could be: neurotransmitter, hormone, stretch, pH

2. Contractility: ability to shorten forcibly when adequately

stimulated.

3. Extensibility: the ability to be stretched

4. Elasticity: ability to recoil & resume original length after being

stretched or contracted. 5
 Muscle Functions
1. Produces Movement of:
 Body parts

 Blood throughout the body

 Food through the GI tract

 Urine through the urinary tract

 Semen through the male and female

reproductive tracts

 A newborn through the birth canal

6
 Muscle Functions..
2. Maintenance of posture

• Muscle contraction is constantly allowing

us to remain upright.

– Muscles of your neck are keeping your

head up right now.

– As you stand, your leg muscles keep you

on two feet.

3. Thermogenesis

– Generation of heat, occurs via shivering. 7

 Muscle Functions..
4. Stabilization of joints:

– Muscles keep the tendons that cross

the joint nice and firm.

– This does a wonderful job of

maintaining the integrity of the joint

8
Types of muscle cells/tissue

9
 Types of muscle ….
1. 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
2. Cardiac muscle:
– Muscle of the heart
– Striated
– Involuntary, controlled by ANS, drugs and hormones
– Have the property of autorhythmicity and syncytium
• due to the presence of pacemaker 10
 Types of muscle ….
3. Smooth muscles

– Located in the wall of hallow organs (GIT, blood vessels,

uterus, urinary bladder, Iris)

– They have non-striated appearance, mononucleated cells

– Involuntary muscle

– Controlled by ANS, drugs and hormones

– Have the property of autorhythmicity and syncytium

11
Types of muscle ….

12
 Skeletal Muscle
• Each muscle fiber in most skeletal muscles:

– Extends the entire length of the muscle.

– Innervated by only one nerve ending,

located near the middle of fiber.

– Supplied by an artery & drained by one

or more veins.

13
Physiologic-anatomy of skeletal muscle

14
Physiologic-Anatomy of skeletal muscle

15
 Skeletal Muscle…physiologic anatomy

• Sarcolemma: plasma membrane of muscle fiber

• Sarcoplasm: cytoplasm of muscle fiber

– Sarcosome: mitochondria of muscle fiber

– Glycogen granules: provide glucose for energy needs

– Sarcoplasmic reticulum (SR): ER of muscle fiber

• functions as calcium storage depot in muscle cells.

• Transverse tubules (T-tubules):

– Invaginations on sarcolemma that penetrate through the

cell 16
 Myofibrils
• Rod like specialized contractile elements of muscle fiber

• Constitute 80% of volume of muscle fiber .

• Compose d of thick & thin myofilaments.

 ~ 1500 myosin filaments and 3000 actin filaments

• A single muscle fiber may contain

• About 16 billion thick and 32 billion thin filaments

17
Myofibrils…

18
 Thick Myofilaments

• Thick myofilament is made of contractile proteins called

myosin

• Single thick filament is made of ~ 300 myosin molecules

• Myosin protein’s tails are intertwined each other and the

heads form crossbridge.

• Each crossbridge has two important sites crucial for

contraction:

1. Actin-binding site

2. Myosin ATPase (ATP-splitting) site 19

Figure. Structure of myosin molecules and their organization within a thick filament.
20
 Thin Myofilaments
• Thin filament is made of 3 different types of proteins:

– Actin, tropomyosin and troponin.

Actin:

• Primary structural proteins of the thin filament

• Each actin molecule has special binding site, for attachment

with myosin crossbridge called myosin binding site

Tropomyosin

• Threadlike proteins those cover myosin binding site of actin

blocking interaction b/n actin and myosin at rest. 21
 Thin Myofilaments…
Troponin

• Trio (triad=three) of protein complex

• Made of three polypeptide units:

 Troponin-C (C- Calcium) = can bind with Ca2+

 Troponin- T (T= tropomyosin) = binds to tropomyosin

 Troponin-I (I- inhibitory) = binds to actin

• When troponin is not bound to Ca2+

– This protein stabilizes Tropomyosin in its blocking position

over actin’s crossbridges binding sites 22
 Thin Myofilaments…

• When Ca2+ binds to troponin,

– Shape of this protein is changed

Tropomyosin slips away from its blocking position.

– Hence, actin and myosin can bind and interact at the cross
bridges, resulting in muscle contraction.

• Tropomyosin and troponin are called regulatory proteins

– Because of their role in covering (preventing contraction) or

exposing (permitting contraction) the binding sites for cross-
bridge interaction between actin and myosin. 23
Thin Myofilaments…

24
Figure. Composition of a thin filament 25
Relation of thick and thin myofilaments

26
 Structural proteins
Titin:
– filamentous proteins connecting myosin to Z disc
– the largest proteins, being made up of nearly 30,000 AA.
Functions of Titin:
– Stabilize the position of the thick filaments
– By acting like a spring, it helps a muscle to passively recoil
to its resting length.
Nebulin:
– An inelastic giant protein
– Lies alongside thin filaments and attaches to the Z disk.
27
– Helps align the actin filaments
 Sarcomeres
• Each myofibril is made up of 1000’s of repeating individual
units known as sarcomeres

• Each sarcomere is an ordered arrangement of thick and thin

filaments. It has:

– regions of thin filaments by themselves

– a region of thick filaments by themselves

– regions of thick filaments and thin filaments overlapping.

28
 Sarcomeres…
• Myosin and actin filaments partially interdigitated and cause
myofibrils to have alternate light and dark bands

• Light or I bands contain only actin filaments

• One I band is actually part of 2 sarcomeres at once.

• Dark bands , contain zone of overlapping and H Zone (only

myosin region), are called A bands.

• M line is at the middle of H zone that helps to hold thick

filaments to one another

29
 Sarcomere…
• Z disk ( line ) passes crosswise across the myofibril attaching
myofibrils to one another all the way across muscle fiber.

Key
• A = anisotropic meaning not light
• I = isotropic , meaning light
• Z = German word Zwischenscheibe, means “between disc.”
• H= German word Hensen’s disc, ?Hell?, meaning “bright” or
clear.
• M= German word Mittelmembran, meaning middle

30
Sarcomeres…

31
Sarcomeres…

32
 Sarcomeres…
Titin structure:

34
 Sarcotubular System = T-Tubules + SR

• Each muscle fiber has many T-tubules

– Typically each myofibril has branch of T-tubule encircling it

at each A-I junction

• At each A-I junction, SR will expand and form dilated sac

called terminal cisterna.

• Each T-tubule will be flanked by a terminal cisterna.

– This forms a triad consisting of 2 terminal cisternae and one

T-tubule branch.

35
Sarco-tubular System…

36
Molecular basis of skeletal Muscle Contraction
“Sliding filament hypothesis”
• Discovered by Hanson & Huxley in 1955

• Is the theory that states inward sliding of the thin filaments,

on each side of a sarcomere , over the stationary thick
filaments toward the A band’s center

• As they slide inward, the thin filaments pull the Z lines to

which they are attached closer together,

• So the sarcomere shortens.

• As all the sarcomeres throughout the muscle fiber’s length

shorten simultaneously, the entire fiber shortens
37
 Sliding filament hypothesis…

38
Figure. Sliding of the thin filaments over thick filaments
 Sliding filament hypothesis…

39
Figure. Structural changes during muscle contraction
Sliding filament hypothesis…

40
 Sliding Filaments…

• All sarcomeres in a fiber will contract together which contracts

the fiber itself.

• Number of fibers contracting will determine force of

contraction of whole muscle.

• Whole process of muscle contraction can have 4 steps:

Step 1. Excitation

Step 2. Excitation-contraction coupling

Step 3. Contraction

Step 4. Relaxation 41
 1. Excitation

• All cells have voltage difference across their plasma

membrane.

– Causes?????

• The value for Vm in inactive muscle cells is typically between

–80 and –90 millivolts.

• Generally each muscle is served by one nerve

• With muscle, each axon will go its own way and eventually
branch into multiple small extensions called telodendria.

42
 Excitation…

• Each telodendria ends in a bulbous swelling known as the

synaptic end bulb

• The site of interaction b/n a neuron and any other cell is known
as a synapse.

• The synapse b/n a neuron and a muscle is known as the

neuromuscular junction

• Minute space b/n synaptic end bulb & sarcolemma is called

synaptic cleft.

43
 Excitation…
• Motor end plate: depression in sarcolemma at synaptic cleft

• The synaptic end bulb is filled with vesicles that contain the
neurotransmitter, acetylcholine

• Motor end plate is chock full of acetylcholine receptors (Ach-R).

44
Excitation…

45
 Excitation…
Characteristics of neuromuscular junction

1. Transmission is unidirectional

2. There is a single NMJ per muscle fiber

3. The neurotransmitter is always acetylcholine (Ach)

4. The post junctional receptor is always nicotinic receptor

5. The effect of Ach on NR is always excitatory producing

EPSP/EPP

6. There is a synaptic delay (0.2 – 0.3 ms)

7. It is fatigable due to depletion of ATP and NT storage 46

NMJ

48
 Excitation…

Factors affecting the NMJ:

NMJ an be affected by various factors

2. Calcium level:

– Hypercalcemia inhibits membrane excitability

– Hypocalcaemia increases membrane excitability

3. Hypoxia:

– inhibits membrane excitability 50

 Excitation…
Factors affecting the NMJ…
3. Drugs:
I. Ach- release inhibitors: Botulin toxin extracted from
Clostridium botulinum- inhibits membrane excitability
II. Nicotinic receptor (cholinergic) blockers: d-tubocurarine, α-
cobratoxin - inhibits membrane excitability
III. Cholinergic stimulants: nicotine, metacholine, carbacholine
- increases membrane excitability
IV. Anti-cholinstrase drugs: Physiostegmin, neostegmin
- increases membrane excitability 51
 Excitation…
Factors affecting the NMJ…
• Hemicholinium-3 (hemi-choline)--drug
– Blocks choline transporter protein on neuron cell membrane
• Vesamicol (drug)
– Blocks acetylcholine transporter protein on the vesicle
• Succinylcholine --drug for general anesthesia
– Continuous stimulation of EPP then decrease responsiveness of V.
gated Na channel – no AP
• Tubocurarine (toxin)
– Blocks nicotinic receptors on motor end plate –paralyzing muscles
52

of the body.
 How Excitation Occurs?

1. Nerve signal arriving at synaptic end bulb will cause

– Ach-containing vesicles to undergo exocytosis.

2. Ach will diffuse across synaptic cleft & bind to Ach receptors

which are ligand-gated Na+ channels.

– Binding of Ach causes opening of Na+ channels.

3. Na+ will rush into cell:

– Making local cell interior more positive (depolarization) but

it is a local event (local potential)= EPP 53

 How Excitation Occurs ...

4. Adjacent to motor end plate, sarcolemma contains voltage-

gated ion channels (Na+ channels)

– In order for these channels to open,

– Vm must depolarize from its resting value of –90mV to

nearly –50mV,

– this is threshold potential.

– This local potential or end plate potential cause action

potential.

54
 How Excitation Occurs…

• Degree of depolarization depends on amount of Na+ influx

• Na+ influx depends on how many Na+ channels were opened

by binding ACh.

• If Vm fails to depolarize to threshold, nothing will happen.

– Vm will soon return to normal & no muscle contraction

• If Vm does reach threshold, 2 types of voltage-gated ion

channels will open:

– Fast Na+ channels and Slow K+ channels

55
 How Excitation Occurs…
• If Vm reaches threshold, fast Na+ channels open and Na+
rushes in causing the Vm to depolarize to +30mV.

• Depolarization stops when Na+ channels become inactivated.

• At this point, slow K+ channels have opened & K+ efflux occurs.

• This returns Vm back to its resting level. This is repolarization.

56
 2. Excitation-Contraction Coupling

• It is the process by which depolarization of muscle fiber

initiates contraction.

• AP travels along sarcolemma going in both directions and

spread down the T- tubules .

• Since T-tubules are simply invaginations of the sarcolemma,

– AP will spread down them

• It is electromechanical mechanism

57
58
 Excitation-Contraction Coupling…
• T-tubular sarcolemma contains voltage sensitive proteins (DHP
receptors) that change their conformation in response to a
significant Vm.

– These are physically linked to Ca2+ releasing channels in SR

– Upon Vm, the voltage sensors change their conformation.

• This mechanically opens Ca2+ channels in SR membrane.

• SR Ca2+ channels are only open briefly, but large Ca2+ gradient
exists so a large amount of Ca2+ enters sarcoplasm.

59
 Excitation-Contraction Coupling…

• Ca2+ interacts with 2 regulatory proteins of sarcomere so that 2

contractile proteins can slide & sarcomere shorten.

• Normally, tropomyosin obstructs myosin binding site on G-

actin subunits.

• Ca2+ binds to troponin-C polypeptide of troponin triad.

• This changes of troponin changes conformation of

tropomyosin, which exposes myosin binding site of actin.

60
 3. Contraction
• Once actin’s myosin binding site is exposed,

– myosin will attach to actin.

– myosin has just hydrolyzed ATP into ADP and Pi –

– both molecules are still bound to the myosin.

– The ATP hydrolysis provides energy for “cocking” of

myosin head.

• Once myosin is bound to actin,

– myosin head will release the ADP and Pi which will cause it
change of conformation. 61
 Contraction…
• This results in thin filament sliding along the thick filament.

• Myosin then remains bound to actin until it binds to another

ATP.

• Myosin then hydrolyzes the new ATP & cycle can begin again.

• The cycle of attachment, power stroke, and release continues as

long as calcium and ATP remain available.

• Typically half the myosin molecules at any time are bound to

the actin while the other half are preparing to bind again.

62
 Contraction…
• A common analogy is climbing a rope hand over hand.

63
64
 Activation pathway for skeletal muscle contraction.
Acetylcholine triggers receptors on muscle cell membrane

Action potential across cell

membrane down T tubules
Troponin returns to its Release of
original conformation Ca2+ from SR
and tropomyosin blocks
myosin head-actin Ca2+ binds to
interactions troponin and
exposes actin
Ca2+ pumped binding sites
back into
sarcoplasmic
reticulum Myosin heads
pull actin along
thick filaments
65

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

66
Excitation-contraction coupling converts an
electrical signal into a calcium signal

68
69
 4. Relaxation

• Ca2+ pumps in SR membrane work constantly to get calcium

out of sarcoplasm and back into SR.

• They are unable to do this as long as muscle is still binding

ACh.

• ACh is released by the motor neuron as long as it keeps being

stimulated.

– ACh does not remain bound to Ach-R for very long.

• It quickly releases and either binds again or

• hydrolyzed by the enzyme acetyl cholinesterase 70

 Relaxation…
• When the muscle ceases being stimulated,

– the calcium pumps “win” and sarcoplasmic [Ca2+] drops.

– Calcium stops being available for troponin and then

– tropomyosin shifts back into its inhibitory position.

• Muscle then

– returns back to its original length via elasticity of connective

tissue elements,

– And the contraction of antagonistic muscles

71
Mechanism of muscle contraction
(Excitation-contraction coupling)-summary
• 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 post junctional membrane. 73
 Mechanism of muscle contraction…
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

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
74
 Mechanism of muscle contraction…
10. The detachment of troponin-I from actin displaces
tropomyosin, 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 movement of the head (power
stroke) towards the centre.

14. The head of myosin is charged with a new molecule of ATP

75
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.

76
 Importance of ATP

• Large amount of energy (ATP) is consumed during muscular

performance for the following activities:

– To move the head of myosin (power stroke)

– Active Ca2+ pump from sarcoplasm to SR

– For Na-K-pump in the membrane

– For muscle relaxation

77
 Motor unit
• Composed of a group of muscle fibers that function together
and the somatic motor neuron that controls them

• When this neuron is stimulated, all the muscle fibers it

synapses upon will be stimulated and will contract as a unit

• The number of muscle fibers per motor unit may be as high as

several hundred or as few as four.

– The smaller the motor unit, the finer and more delicate the
movements.

– Extraocular muscles typically have small motor units while

78
large postural muscles have large motor units
Motor unit..

80
 Muscle Twitch
• A muscle twitch is the response of the muscle fibers to a single
action potential. i.e.

– A single contraction-relaxation cycle

– The fibers contract quickly and then relax.

• Phases of the Muscle Twitch

– Latent Period

• Time b/n stimulus and generation of tension

– Contraction

– Relaxation 81
Twitch Contraction

48
82
measurement of a neuron’s AP, a muscle fiber’s AP, and the tension developed by that muscle
83
fiber.
 Strength of muscle contraction
• This depends on the

– number of muscle fibers contracting within a muscle

– extent of motor unit recruitment

– tension developed by each contracting fiber

• To prevent fatigue the body alternates motor unit activity, like

shift s at a factory, to give motor units that have been active an
opportunity to rest while others take over.

• Changing of the shift is carefully coordinated,

– so the sustained contraction is smooth rather than jerky. 84

 Factors determining Whole-muscle
tension

1. Frequency of stimulation

2. Length of the fiber at the onset of contraction

3. Extent of fatigue

4. Thickness of the fiber

85
 1. Frequency of stimulation…
• If the muscle fiber has completely relaxed before the next action
potential takes place, a second twitch of the same magnitude as the
first occurs (see Fig below) results in identical twitch responses.

• If, however, the muscle fiber is stimulated a second time before it has
completely relaxed from the first twitch, a second action potential
causes a second contractile response, which is added “piggyback” on
top of the first twitch.

• The two twitches from the two action potentials add together, or
sum, to produce greater tension in the fiber than that produced by a
single action potential. This is called twitch summation
86
 1. Frequency of stimulation…

• Twitch summation is possible only because the duration of the

action potential (1 to 2 msec) is much shorter than the duration
of the resulting twitch (100 msec)

• If the muscle fiber is stimulated so rapidly that it does not have

a chance to relax at all between stimuli, a smooth, sustained
contraction of maximal strength known as tetanus occurs.

• A tetanic contraction is usually three to four times stronger

than a single twitch. (Don’t confuse this normal physiologic
tetanus with the disease tetanus
87
88
 1. Frequency of stimulation…
• If the stimuli are of moderate frequency just below the
minimum tetanic frequency, and each stimulus falls in the
relaxation phase, the result is a series of contraction with
incomplete relaxation.

• This type of contraction is called clonic contraction, clonus or

incomplete tetanus

• Twitch summation results from a sustained elevation in

cytosolic calcium permitting greater cross-bridge cycling and
from increased time to stretch the series-elastic component.
89
 2. Length of the fiber at the onset of
contraction
• There is an optimal muscle length at which maximal tension can be
developed.

• AT OPTIMAL LENGTH (lo) At lo, when maximum tension can be

developed (point A in ● Fig below), the thin filaments optimally
overlap the regions of the thick filaments from which the cross
bridges project.

• At this length, a maximal number of cross bridges and actin

molecules are accessible to each other for cyles of binding and
bending

• The central region of thick filaments, where the thin filaments do not
90
overlap at lo, lacks cross bridges; only myosin tails are found here
2. Length of the fiber at the onset of contraction…

91
 Types of Contractions

• Contractions can be:

– Isometric

• Iso= same, metr=measure

– Isotonic

• Iso=same, ton=tension

92
 Isotonic Contraction
• It is the type of contraction with no change in muscle tension

• There is shortening of the total Length of the muscle

• Occurs when contraction moves an object of moderate Weight

• Work is done in this type of contraction

93
 Isotonic Concentric:
flexion
Contraction (muscle
shortens)

Generates movement

Concentric: flexion
(muscle shortens)

Eccentric: extension
(muscle lengthens) 94

70
 Isometric Contractions
• It is the type of contraction with out change in Length

• Occurs when muscle contraction fails to move heavy objects

• No work is done in this type of contraction

95
 Isometric
Contraction

No movement

Maintains posture

Maintains objects in
fixed position 96

71
 Skeletal Muscle Metabolism and Fiber
Types
• Three different steps in the contraction–relaxation process
require ATP

1. Splitting of ATP by myosin ATPase provides the energy

for the power stroke of the cross bridge.

2. Binding of a fresh molecule of ATP to myosin lets the

bridge detach from the actin filament at the end of a power
stroke so that the cycle can be repeated.

– This ATP is later split to provide energy for the next

stroke of the cross bridge.
97
 Skeletal Muscle Metabolism…
3. Active transport of Ca2+ back into the sarcoplasmic reticulum

during relaxation depends on energy derived from the

breakdown of ATP.

• At rest ATP is also utilized by sodium potassium pump to

maintain resting membrane potential

98
99
Muscle fibers have alternate pathways for
forming ATP.
• Only limited stores of ATP are immediately available in muscle
tissue,

• But three pathways supply additional ATPase needed during

muscle contraction:

1. Transfer of a high-energy phosphate from creatine

phosphate to ADP

2. Oxidative phosphorylation and

3. Glycolysis

100
101
 1. Creatine phosphate
• Creatine phosphate is the first energy storehouse tapped at the
onset of contractile activity

• Just as energy is released when the terminal phosphate bond in

ATP is split, similarly energy is released when the bond b/n
phosphate and creatine is broken.

• The energy released from the hydrolysis of creatine phosphate,

along with the phosphate, can be donated directly to ADP to
form ATP.

• This reaction is catalyzed by the muscle cell enzyme creatine

102
kinase.
 2. Oxidative phosphorylation
• If the energy-dependent contractile activity is to continue

• takes place within the muscle mitochondria if sufficient O2 is

present.

• This pathway is fueled by glucose or fatty acids, depending on

the intensity and duration of the activity

• yield of 32 ATP molecules for each glucose but slow process.

• muscle cells can form enough ATP through oxidative

phosphorylation during light exercise (such as walking) to
moderate exertion such as jogging or swimming
103
 3. Glycolysis
• There are respiratory and cardiovascular limits to how much O2
can be delivered to a muscle.
– That is, the lungs and heart can pick up and deliver just so much
O2 to exercising muscles.

• Furthermore, in near-maximal contractions, the powerful

contraction compresses almost closed the blood vessels that
course through the muscle,

– severely limiting the O2 avail able to the muscle fibers.

104
 3. Glycolysis…
• Even when O2 is available, the relatively slow oxidative-
phosphorylation system may not be able to produce ATP
rapidly enough to meet the muscle’s needs during intense
activity.

• A skeletal muscle’s energy consumption may increase up to

100-fold when going from rest to high intensity exercise

• Glycolysis alone has two advantages over the oxidative

phosphorylation pathway:

1. Operates anaerobically
105
2. proceed more rapidly than oxidative phosphorylation.
 3. Glycolysis…
• Lactate production

– when the end product of an aerobic glycolysis, pyruvate,

cannot be further processed by the oxidative
phosphorylation pathway, it is converted to lactate.

– Lactate accumulation has been implicated in the muscle

soreness that occurs during the time that intense exercise is
actually taking place.

• The delayed-onset pain and stiff ness that begin the day
after unaccustomed muscular exertion, however, are
106
probably caused by reversible structural damage.
 Muscle Fatigue
• Occurs when an exercising muscle can no longer respond to
stimulation.

• Physiological inability to contract

• Possible causes of muscle fatigue

– Local increase in ADP and Pi

– Accumulation of lactate

– Accumulation of extracellular K+

– Depletion of glycogen energy reserves

107
 Muscle Fatigue…
• Physiological inability to contract. Types:

– Psychological (central) fatigue

• Feeling of tiredness and a desire to stop

• Depends on emotional state of individual

– Muscular

• Depletion of glycogen energy reserve

– Synaptic

• Occurs in NMJ due to lack of acetylcholine

108
 Oxygen Debts
• Refers to the fact that post-exercise breathing rate > resting
breathing rate.

• This excess oxygen intake serves many tasks:

– Replenish the oxygen stored by myoglobin and hemoglobin

– Convert remaining lactic acid back into glucose

– Used for aerobic metabolism to make ATP which is used to:

• Replenish the phosphagen system

• Replenish the glycogen stores

• Power the Na+/K+ pump so as to maintain RMP 109

 Types of Skeletal Muscle Fibers
• Based on major pathways used to form ATP and fatigability,

– Oxidative fibers – use aerobic pathways

– Glycolytic fibers – use anaerobic glycolysis

• Muscle fibers are classified into 3 types as

– Type-I: Slow, fatigue-resistant, oxidative fibers.

– Type-II a: fast, fatigue-resistant, oxidative fibers.

– Type-IIx: fast, fatigable, glycolytic fibers. 110

 Types of Skeletal Muscle Fibers...
• Fast/glycolytic fibers have:
– Myosin with high ATPase activities
– High content of glycolytic enzymes
– Large storage of glycogen
– Little myoglobin contents
– Few mitochondria
• Slow oxidative fibers have:
– Myosin with low ATPase activities
– Numerous mitochondria
– High capacity of oxidative phosphorylation
– Rich in arterial blood supply, high BF
111
– Large amount of myoglobin contents
Table. Characteristics of Skeletal Muscle
Fibers

112
 Slow
Oxidative
(SO) Fibers

Smallest, weakest,
slowest (slow-
twitch)
Red muscle: lots
of mito, myo, &
blood
Aerobic cellular
respiration  ATP
113

74
 Slow
Oxidative (SO)
Fibers…
Sustained
contractions

High fatigue
resistance

Maintains posture,

Aerobic endurance
activities (marathon
running) 114

75
 Fast
Oxidative-
Glycolytic
(FOG) Fibers
Aerobic &
anaerobic
respiration 
ATP (store
glycogen)
Moderate
fatigue
resistance
Walking,
sprinting 115

77
 Fast
Glycolytic
(FG) Fibers

Largest, strongest,
fast twitch

High glycogen
storage

White muscle: less

mito, myo, blood 116

78
 INFLUENCE OF TESTOSTERONE
• Men’s muscle fibers are thicker, and accordingly, their
muscles are larger and stronger than those of women, even
without weight training,
– because of the actions of testosterone, a steroid hormone
secreted primarily in males.
• Testosterone promotes the synthesis and assembly of myosin
and actin.
• This fact has led some athletes, both males and females, to the
dangerous practice of taking this or closely related steroids to
increase their athletic performance. 117
 Muscular Adaptation
Hypertrophy: Increase in size of a cell, tissue or an organ.

• Muscle hypertrophy occurs due to the synthesis of more

myofibrils and synthesis of larger myofibrils.

• Resulting from very forceful, repetitive muscular activity.

 More capillaries
 More mitochondria
Caused by:
 Strenuous exercise
 Steroid hormones such as testosterone
118
 stimulate muscle growth and hypertrophy
 Muscular Adaptation…

• Atrophy : Reduction in size of a cell, tissue, or organ

• In muscles, its often caused by disuse.

119
 Muscular Disorders
• Rigor Mortis

– Upon death, muscle cells are unable to prevent Ca2+ 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.

• Cramp: prolonged spasm that causes muscle to become taut

and painful

• Fibrosis : Replacement of normal tissue with heavy fibrous

120

connective tissue (scar tissue).

 Muscular Disorders…
• Myasthenia Gravis:

– My=muscle, asthen=weakness, gravi=heavy

– Autoimmune disease where antibodies attack the ACh

receptors on neuromuscular junctions.

– Results in progressive weakening of skeletal muscles.

– Treated by Anticholinesterase agents such as neostigmine

Inhibits AChE temporarily and

Prolongs the action of ACh at the NMJ to initiate an

AP and subsequent contraction in the muscle fiber121
 Muscular Disorders…
Myasthenia Gravis

122
 Muscular Disorders…
Eaton Lambert syndrome
– Auto immune destruction of Ca2+ channel on pre-SM
Organophosphate poisoning
– OPs are Chemicals that irreversibly inhibit AChE.
• Prevent the inactivation of ACh.
• Normally ACh rapidly hydrolyze in to inactive fragments of
choline and acetic acid.
– Death occurs due to respiratory failure
• b/c the diaphragm cannot repolarize and return to
resting conditions, then contract again 123
 Muscular Disorders…
Botulism:
• Caused by Clostridium botulinum found in improperly
canned food
• When the toxin of the bacteria is consumed,
– blocks release of Ach at the NMJ by inhibiting the action
of proteins (synaptobrevin & syntaxin) on presynaptic
membrane.
– It prevents muscles from responding to nerve impulses.
– Muscle contraction can not occur.
• Death is due to respiratory failure caused by inability to
124
contract the diaphragm(paralysis of the diaphragm)
 Smooth muscle
• Involuntary, non-striated muscle tissue

• Occurs within almost every organ, forming sheets, bundles,

• In Cardiovascular system:

– Smooth muscle in blood vessels regulates blood flow

through vital organs.

– Smooth muscle also helps regulate blood pressure.

125
 Smooth muscle…

• Digestive systems:

– Rings of smooth muscle, called sphincters, regulate mov’t

along internal passageways.

– Smooth muscle lining passageways alternates contraction

and relaxation to propel matter through alimentary canal.

• Integumentary system:

– Regulates blood flow to the superficial dermis

– Allows for piloerection

126
 Smooth muscle …
• Respiratory system

– Alters the diameter of the airways and changes the

resistance to airflow

• Urinary system

– Sphincters regulate the passage of urine

– Move urine into and out of the urinary bladder

127
 Smooth muscle…
Reproductive system

Females

– Assists in mov’t of the egg (and of sperm) through the

female reproductive tract

– Plays a large role in childbirth

Males

– Allows for mov’t of sperm along reproductive tract

– Allows for secretion of non-cellular parts of semen

– Allows for erection and ejaculation. 128

 Smooth muscle cells
• Are uninucleate: contain 1 centrally placed nucleus

• Lack T-tubules

• Have a scanty sarcoplasmic reticulum

• Smooth muscle tissue is innervated by the autonomic nervous

system

• Myosin and actin are present and crossbridges formation

powers contraction,

• but the thick and thin filaments do not have the strict
repeating arrangement like that found in skeletal muscle
129
 Smooth muscle cells

• No Z discs, instead thin filaments are attached to protein

structures called dense bodies which attach to the sarcolemma.

130
 Types of Smooth Muscle

• Smooth muscle varies widely from organ to organ in terms of:

– Fiber arrangement

– Responsiveness to certain stimuli

• Broad types of smooth muscle:

– Single unit

– Multi unit

131
 Single Unit Smooth Muscle (SUSM)
• More common

• Cells contract as a unit b/c all connected by gap junctions.

• AP can propagate through neighboring muscle cells due to gap

junctions.

• Due to this property, SUSM bundles form a syncytium that

contracts in a coordinated fashion

– such as uterine muscles contraction during childbirth

• Commonly found in the walls of the digestive tract, urinary

bladder, and uterus
132
Single Unit Smooth Muscle (SUSM)…

133
 Characteristics of Single Unit Smooth Muscles

• Innervated by an autonomic nerve fiber.

• SUSM is myogenic;

– it can contract regularly without input from a motor neuron

• A few of the cells in a given SUSM unit may behave

– pacemaker cells, generating rhythmic action potentials due

to their intrinsic electrical activity.

134
 Multi-Unit Smooth Muscle
• No gap junctions.

• Contraction of each fiber is independent of all the others.

• Responsible to neural & hormonal controls

• Less common and have no pacemaker cells

• It is neurogenic

– its contraction must be initiated by motor neuron.

• Found in

– large airways (lungs), large arteries, arrector pili, internal

eye muscles 135
 Smooth Muscle Contraction
• Begins with opening of membrane channels.

• Channels may be ligand (NTs, hormones ), voltage, or

mechanically-gated (stretch).

• Channels will allow significant calcium entry from ECF.

– Smooth muscle has little SR.

• Ca2+ binds to regulatory molecule called calmodulin and

activates it.

• Activated calmodulin activates an enzyme called Myosin Light

Chain Kinase (MLCK). 136
 Smooth Muscle Contraction…
• Activated MLCK will add a phosphate group to the myosin of
thick filament.

• This enables myosin to interact with actin.

• Tropomyosin is present but not blocking actin’s myosin

binding sites

• Troponin is absent

137
Smooth Muscle Contraction…

138
 Smooth Muscle Relaxation

• For smooth muscle to relax

– Ca++ ions must be removed from the intracellular fluids by a

calcium pump back into the

A. ECF, or

B. Into sarcoplasmic reticulum

– This pump is slow-acting

• Accounts for prolonged contraction 143

Smooth Muscle Relaxation

144
 Cardiac Muscle
• Provides the motive power for blood circulation

• Striated, involuntary muscle

• Found in walls of the heart

• Consists of branching chains of stocky muscle cells.

• Uni- or binucleate.

• Has sarcomeres & T-tubules

• Are joined by structures called intercalated discs

– which consist of desmosomes and gap junctions.

145
Cardiac Muscle…

146
Cardiac Muscle
Intercalated disc

147
 Cardiac Muscle…
• Intercalated discs have 2 components.
– Gap junctions (which provide an electrical link between all
cardiac myocytes) and
– Desmosomes (which provide a mechanical link between all
cardiac myocytes).
• The electrical & mechanical connections created by the
intercalated discs allow the thousands of cardiac muscle cells to
behave as if they were one giant cell.
• Multiple cells that function as one entity are often referred to as
a functional syncytium. 148
Cardiac Muscle…

149
 Cardiac Muscle…
• All cardiac myocytes are not identical.

• 99% of cardiac wall is composed of the contractile cardiac

muscle cells.

– they generate the force that pumps blood through the

systemic and pulmonary circuits.

• 1% are the autorhythmic cells (pacemakers) of the heart.

– lack the elaborate sarcomeres & other contractile machinery.

– specialized to generate action potential spontaneously and

without nervous system input.
150
 Cardiac muscle…
• Do not contract unless stimulated electrically by pacemaker
tissue

• Less abundant but larger size T tubules

• Less developed SR

– Smaller intracellular reserve of Ca++, cardiac muscle cells

need additional Ca from ECF for contraction

– 90% of calcium source for contraction is from SR and

10% is from ECF

151
Excitation-contraction coupling in cardiac muscle

• Mechanism by which AP causes contraction of myocardium

• Calcium ions provide the link b/n electrical excitation &

muscle contraction

• Influx of Ca2+ from ECF during excitation (plateau) triggers

release of Ca2+ from SR.

• Free cytosolic Ca2+ activates contraction of myofilaments

(systole) 152
Excitation-contraction coupling in cardiac muscle

• Relaxation (diastole) occurs as result of uptake of Ca2+ by SR &

extrusion of intracellular Ca2+ by Na+-Ca2+ exchange

• Sequences

– Auto-rhythmicity → Membrane depolarization →T-tubule

depolarization→ Release of Ca2+ from SR + from T-tubule

(ECF)→ Ca2+ activates contractile molecules →Sliding of

filaments→ Contraction
153
Excitation-contraction coupling: cardiac muscle

154
Excitation-contraction coupling: cardiac muscle…

155
Fig: EC coupling and relaxation in cardiac muscle cells
 Cardiac muscle syncytium

• B/c cardiac cells are joined by gap junctions, AP propagates

from cell to cell

• Muscle cells contract as unit ( syncytium)

• Atrial syncytium: All atrial cells excite and contract together as

a unit

• Ventricular syncytium: All ventricular cells excite and contract

together as a unit 156

 Electromechanical Properties of Heart
• Heart continues to beat after full denervation b/c of intrinsic
properties it has:

A. Automaticity : start pacemaking

A. Conductivity: highly developed in PNW

B. Contractility: Atrial & ventricular muscles are specialized for

contraction

C. Refractoriness :

– Cardiac cell is unresponsive to further stimuli

– The AP of cardiac muscle has a prolonged refractory period

157
 Electrical activity of cardiac cells…
• Ionic basis of cardiac AP is associated with changes in
– permeability of cell membrane to: Na+, K+, and Ca2+ ions.
• Ionic basis of myocardial AP has 5-phases.
 Phase-0: Rapid depolarization caused by rapid Na-influx
 Phase-1: initial repolarization caused by fast K+ channel
opening
 Phase-2: plateau caused by Ca2+ influx
 Phase-3: rapid Repolarization caused by slow potassium
channel opening K+ efflux
 Phase-4: resting state
• RMP is re-established by Na-K-ATPase.
NB- RMP = -90 mv 158
159
Electrical activity of cardiac cells…

160
Comparison of 3 muscle types

161
Thank you !!!!!

162