Physiology U-4 Excitable Muscle Tissue

Excitable Tissue: Muscu-
lar Tissue
Physiology
Unit
1
Outline
 Muscle Tissue
Types of Muscles
Characteristics of Muscle Tissue
Functions of Muscles
Structure of Skeletal Muscles
 Muscle Contraction
 Muscle Metabolism
 Types of Skeletal Muscle Fibers
 Muscle Hypertrophy and Atrophy
 Muscle Fatigue
 Cardiac Muscle
 Smooth Muscle
2
Objectives
 Compare the similarities and differences among types of muscles
 Describe the structural organization of skeletal muscle
 List proteins that form thick and thin filaments
 Describe structural components of sarcomere
 Explain mechanism of muscle contraction (Excitation-contraction
coupling)
 Discuss molecular bases of muscle contraction
 Describe the reactions by which muscle fibers produce ATP.
3
Muscle Tissue
 Muscle cells have a special capacity to utilize chemical energy
(ATP) to produce force and movement that enable us to manipulate
objects around us.
 Muscle cells are highly specialized cells for the conversion of chem-
ical energy into mechanical energy.
 Specifically, muscle cells use the energy in ATP to generate force or

to do work.
 About 40% of the body weight is skeletal muscle & 10% is smooth
& cardiac muscle.
4
Types of Muscles
 Muscles are grouped into three major categories according to:
Their location in relation to other body structures
Their histological (tissue) structure
The way their action is controlled
 These classifications are:
A.Skeletal muscle
B.Cardiac muscle
C.Smooth muscle
5
Types of Muscles…
A. Skeletal/voluntary muscles:
Located attached to bones & moves skeleton.

They are elongated, cylindrical and multinucleated cells.
They are striated muscles (alternating light and dark bands within
the fibers that are visible under a light microscope).
They are voluntary muscles (their activity can be consciously con-
trolled by neurons that are part of the somatic (voluntary) division of
the nervous system).
6
Types of Muscles…
B. Cardiac muscle:
Forms the wall of the heart
They are striated
They are involuntary, controlled by autonomic nervous sys-
tem
Have the property of autorhythmicity and syncytium
Motive power for blood circulation (provides force for mov-
ing blood throughout the body)
C. Smooth muscles:
Located in the wall of hallow organs (gastrointestinal tract,
blood vessels, uterus, urinary bladder)
They have non-striated appearance
Involuntary muscle, controlled by autonomic nervous system
7
Have the property of autorhythmicity and syncytium
Types of Muscles…
8
Types of Muscles…
9
Characteristics of Muscle Tissue:
Electrical excitability
 Is the ability to respond to certain stimuli by producing
electrical signals called action potentials.
Contractility
 Ability to shorten in length.
Extensibility
 Ability to stretch without being damaged.
Elasticity
 Is the ability to return to its original length and shape after
contraction or extension.
10
Functions of Muscles:
Producing body movements
 Movements of the whole body such as walking and running, and
localized movements such as grasping
Storing and moving substances within the body
 Temporary storage of food in the stomach or urine in the urinary
bladder
 Movement of body parts
 Movement of blood throughout the body
 Movement of lymph through the lymphatic vessels
 Movement of food through the GI tract
 Movement of bile out of the gallbladder and into the digestive
tract
 Movement of urine through the urinary tract
 Movement of semen through the male and female reproductive
tracts
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 Movement of a newborn through the birth canal
Functions of Muscles:
Maintain posture
 Muscle contraction is constantly allowing us to remain upright.
 Contractions of your neck muscles hold your head upright.
 As you stand, your leg muscles keep you on two feet.
Stabilize joints
 Muscles keep the tendons that cross the joint nice and firm.
 This does a wonderful job of maintaining the integrity of the
joint.
Thermogenesis (Heat production)
 Generation of heat. Occurs via shivering – an involuntary con-

12
traction of skeletal muscle.
Structure of Skeletal Muscles
 A single skeletal-muscle cell is known as a muscle fiber.
 The term muscle refers to a number of muscle fibers bound to-

gether by connective tissue.
 The relationship between a single muscle fiber and a muscle is

analogous to that between a single neuron and a nerve, which is
composed of the axons of many neurons.
13
Structure of Skeletal Muscles…
 Skeletal muscle consist of numerous subunits or bundles called fas-
cicles (muscle fascicles).
- Surrounded by connective tissue (called the perimysium)
 Each fascicle is composed of numerous muscle fibers (muscle cells)
which is covered with endomysium.
 Muscle fibers contains several hundreds to thousands of myofibrils

 Myofibrils are made up of myofilaments
 The two types of myofilaments are thick filaments & thin filaments
which are large polymerized protein molecules that are responsible
for the actual muscle contraction.
14
Structural organization of skeletal muscle
Entire muscle
Muscle fascicles
Muscle fibers
Myofibrils
thin filament (actin, troponin & tropomyosin)
Myofilaments
thick filament (myosin)
15
16
17
Connective Tissue Components of Skele-
tal Muscle…
 Three layers of connective tissue extend from the fascia to protect
and strengthen skeletal muscle:
 Epimysium – is the outermost layer which surrounds entire muscle.
 Perimysium – is a connective tissue which surrounds muscle fasci-
cules (bundle of muscle fiber)
Surrounds groups of 10 to 100 or more muscle fibers, separating
them into bundles called muscle fascicles.
 Endomysium – is a connective tissue which surrounds individual
muscle fiber
A thin sheath of connective tissue separating individual muscle
fibers from one another.
18
Connective Tissue Components of Skele-
tal Muscle…
19
Microscopic Organization of Skeletal
Muscle Fiber
 The number of skeletal muscle fibers is set before you are
born, and most of these cells last a lifetime.
 The diameter of a mature skeletal muscle fiber ranges from 10

-100µm.
 The typical length of a mature skeletal muscle fiber is 10 cm.
 Each mature skeletal muscle fiber has a hundreds or more nu-

clei.
20
Muscle Fiber…
Sarcolemma
 The plasma membrane of a muscle cell.
 Thousands of tiny invaginations of the sarcolemma, called

transverse (T) tubules.
 Muscle action potentials travel along the sarcolemma and

through the T-tubules.
21
Muscle Fiber…
 T-tubules are invaginate from the sarcolemma toward the cen-
ter of the muscle fiber.
 T-tubules are open to the outside of the fiber and thus are filled
with interstitial fluid.
22
Muscle Fiber…
Structures of skeletal muscle cell

23
Muscle Fiber…
Sarcoplasm
 The cytoplasm of a muscle fiber.
 The space b/n the myofibirls are filled with intracellular fluid
called sarcoplasm.
 Has lots of mitochondria, glycogen granules (to provide glu-
cose for energy needs) as well as myofibrils and sarcoplasmic
reticulum.
 Contains a red-colored protein called myoglobin found only in
muscle, and binds oxygen molecules.
24
Muscle Fiber…
Sarcoplasmic reticulum
 Muscle cell version of the
smooth endoplasmic retic-
ulum.
 Surrounds myofibrils and

is closely associated with
transverse tubules.
 Its function is to store cal-

cium ions (Ca2+).
25
Muscle Fiber…
 A muscle cell has two tubular
structures:
a. Transverse tubules (T-tubules)
Function: conduction of depolar-
ization.
b. Longitudinal tubules (smooth en-
doplasmic reticulum)
Function: Ca2+ storage
26
Microscopic Organization of Skeletal Mus-
cle Fiber…
 Each muscle fiber has
many T-tubules
Typically each
myofibril has a
branch of a T-
tubule encircling
it at each A-I
junction
 At each A-I junction,
the SR will expand
and form a dilated
sac (terminal cis-
terna). Each T-tubule will be flanked by a ter-
minal cisterna. This forms a so-called
triad consisting of two terminal cister-
nae and one T-tubule branch.
27
Muscle Fiber…
28
Myofibrils
 Are contractile organelles (machinery) of skeletal muscle
fibers.
 Are about 2µm in diameter and extend the entire length of a

muscle fiber.
 Each muscle fiber contains several hundred to several thou-

sand myofibrils.
29
Myofibrils…
 Each myofibril is made up 1000’s of repeating basic functional

units (compartments) known as sarcomeres.
 Each sarcomere is an ordered arrangement of thick (myosin)

and thin (actin) filaments which are responsible for the actual
muscle contraction.
 Sarcoplasmic reticulum wraps around each myofibril.
30
Myofilaments
Thin myofila- Thick myofila-

ment ment
 Two types of myofilaments which make up myofibrils:

 Thin myofilament
 Thick myofilament
31
Thin filaments
 Composed of 3-proteins
• Actin Contractile Pro-

tein
Regulatory
• Tropomyosin
Proteins
• Troponin
Troponin has 3-parts
1. Troponin-C
2. Troponin-I
3. Troponin-T
32
Thin filaments…
 Each thin filament is made up of 3 -types of proteins:
actin, tropomyosin, & troponin.
Each thin filament consists of a long helical double strand. This

strand is a polymer that resembles a string of beads. Each “bead”
is the globular protein actin. On each actin subunit, there is a
myosin binding site.
Loosely wrapped around the actin helix & covering the myosin
binding site is the filamentous protein, tropomyosin.
Bound to both actin & tropomyosin, there is a trio of proteins col-

lectively known as troponin.
33
Thin filaments…
 Troponins are attached intermittently along the sides of the
tropomyosin molecules.
 They are complex of three loosely bound protein sub-units

which play specific role in controlling muscle contraction.
 This complex is believed to attach the tropomyosin to actin

The strong affinity of the troponin for Ca++ is believed to ini-
tiate the contraction process.
34
Thin filaments…
Actin
The basic components of each thin filament are actin

monomers called G-actin, each of which has a myosin-binding
site (active site).
G-actins are linked together end to end, like pearls in a neck-

lace, to form strands called F-actin (fibrous proteins).
Two F-actins are arranged in a double helix to form the actin

strands found in thin filaments.
35
Thin filaments…
 Thin filaments contain two regulatory proteins that enable

muscle fibers to start or stop contracting; tropomyosin and
troponin.
Tropomyosin
 Is a long fibrous molecule that extends over numerous actin
monomers.
 It blocks the myosin-binding sites in muscles at rest.
 Prevents cross bridge cycling until it is moved aside by tro-
ponin.
36
Thin filaments…
Troponin
Troponin is a complex of three proteins attached intermittently
along the sides of the tropomycin molecules.
Troponin-I (has strong affinity for actin)
Troponin-T (has strong affinity for tropomyosin)
Troponin-C (has strong affinity for Ca++)
Troponin is a three-polypeptide complex that binds calcium ions
and “drags” tropomyosin off the myosin binding sites on actin.
37
Thick filaments
 Thick myofilaments are composed of the protein myosin.
 A single myosin protein

resembles 2 golf clubs Myosin
whose shafts have been
twisted about one another
 About 300 of these
myosin molecules are
joined together to form
a single thick filament
 The head of myosin
function as ATPase en-
zyme.
 The tail forms the body
of myosin filament. 38
Thick filaments
 Thick filaments are located in the middle of each sarcomere
and about 300 myosin molecules are joined together to form a
single thick filament.
 Thick filaments orderly parallel arrangement produces a
wide, dark band known as the A-band.

 Myosin molecules bind to each other at their tail ends so that
their heads extend in opposite directions away from the center.
 Because the middle of the thick filament is devoid of cross-

bridges, this region is called the bare zone.
39
Thick filaments…
 Each myosin molecule is a dimer consisting of two inter-

twined subunits, each having a long tail and a fat, protruding
head.
 The heads of myosin molecules are called “crossbridges” be-

cause they bridge the gap between the thick and thin filaments
during muscle contraction.
 The head is the “business end” of the myosin molecule—it is

the part that actively generates a muscle’s mechanical force.
40
Thick filaments…
Composed of a "protein myosin"
Myosin has 3-parts
Head
Tail
Hinge
41
Thick filaments…
Characteristics of the Myosin Head:
 Myosin head has "ATP-binding sites"
 ATP  ADP + Pi + energy.
42
Thick filaments…

Myosin head has "Actin-binding sites", w/c fits with actin molecules.
43
Thick filaments…

Myosin has a "hinge"
w/c allows the head to rotate back & forth.
44
Summary Skeletal Muscle Fibers Proteins
 Contractile proteins - proteins that generate force during muscle
contractions.
Myosin – a contractile protein that makes up the thick filament. A
myosin molecule consists of a tail and two myosin heads, which bind to
myosin-binding sites on actin molecules of a thin filament during muscle
contraction.
Actin – a contractile protein that is the main component of the thin fila-
ment. On each actin molecule is a myosin-binding site where a myosin
head of a thick filament binds during muscle contraction.
 Regulatory proteins - proteins that help switch the muscle contrac-
tion process on and off.
 Tropomyosin - regulatory protein that is a component of the thin filament.
myosin-bind-
 When a skeletal muscle fiber is relaxed, tropomyosin covers the
ing sites on actin molecules, thereby preventing myosin from binding to
actin. 45
Summary Skeletal Muscle Fibers Proteins
Troponin - regulatory protein that is a component of the thin filament.
 When calcium ions (Ca2+ ) bind to troponin, it undergoes a change in shape; this
conformational change moves tropomyosin away from myosin-binding sites on
actin molecules, and muscle contraction subsequently begins as myosin binds to
actin.
 Structural proteins - proteins that keep the thick and thin filaments of the my-
ofibrils in proper alignment, give the myofibrils elasticity and extensibility, and
link the myofibrils to the sarcolemma and extracellular matrix.
Titin - structural protein that connects a Z disc to the M line of the sarcomere, thereby
helping to stabilize the position of the thick filament. Because it can stretch and then
spring back unharmed, titin accounts for much of the elasticity and extensibility of my-
ofibrils.
46
Thick and thin filament
47
Microscopic Organization of Skeletal Muscle
 When viewed under microscope skeletal muscle cells have a
striped appearance (striated muscle).
 These striations are due to the orderly arrangement of protein

fibers in the myofibrils called thick and thin filaments which
run parallel to the muscle cell’s long axis.
 The thin and thick filaments exist in a 2:1 ratio.
48
Microscopic Organization…
 Each sarcomere is bordered on either end by Z disc, which run
perpendicular to the long axis and anchor the thin filaments at
one end.
 The Z disc is composed of filamentous proteins different from

the actin and myosin filaments.
 The Z disc proteins pass crosswise across the myofibril and

also crosswise from myofibril to myofibril, attaching the my-
ofibrils to one another all the way across the muscle fiber.
49
 The thick filaments in a sarcomere are connected by M lines
(middle of sarcomere), which also run perpendicular to the
long axis.
 M-line is the middle of the H zone and functions to hold the

thick filaments to one another.
 The portion of the sarcomere which contains the thick filament

is known as the A band (appears dark under the microscope).
50
 The A band contains a zone of overlap between thick & thin
filaments .
 The portion of the sarcomere which does not contain any thick
filament is known as the I band.
 The I band contains only thin filament and is light under the
microscope and actually part of two sarcomeres at once.
 H zone contains only thick filaments.
51
52
53
Sarcomere within myofibrils
54
55
Components of the Sarcomere
 Z discs - narrow, plate-shaped regions of dense material that sep-
arate one sarcomere from the next.
 A band/The dark - middle part of the sarcomere that extends the
entire length of the thick filaments and also includes those parts
of the thin filaments that overlap with the thick filaments. A
stands for anisotropic which is a fancy way of saying that it ap-
pears dark under the microscope.
 I band/ The lighter - less dense area of the sarcomere that con-
tains the rest of the thin filaments but no thick filaments. It is
light under the microscope (it is isotropic).
Z disc passes through the center of each I band.
 H zone - A narrow region in the center of each A band that con-
tains thick filaments but no thin filaments.
 M line - A region in the center of the H zone that contains pro-
teins that hold the thick filaments together at the center of the 56
Muscle Contraction: The Sliding Filament Hypothesis
 Hanson & Haxley proposed that the skeletal muscles shorten dur-
ing contraction because;
The thin filaments slide over the thick filaments.
This pulls the Z-discs close together.
When all the sarcomeres in a fiber do this, the entire fiber gets
shorter which pulls on the endomysium, perimysium, epimy-

sium & attached tendon and then pulls on the bone.
57
Muscle Contraction: The Sliding Filament Hypothesis…
Here is what happens

as the filaments slide
and the sarcomere and
the muscle fiber shortens.
In the process of contraction:
1. Distance b/n Z discs -
shorten
2. Length of the A band –
do not
shorten
3. Length of the H zone -
shorten
4. Length of the I band-
shorten
58
Muscle Contraction: The Sliding Filament Hypothesis…
 Hanson and Haxley proposed that the skeletal muscles shorten during
contraction b/c the thick and the thin myofilaments slid past one
another. Their model is known as the sliding filament mechanism
of muscle contraction.
59
Muscle Contraction
The whole process of muscle contraction is divided
into 4 steps:
Excitation
Excitation-contraction coupling
Contraction
Relaxation
60
Excitation
 In general each muscle is served
by one nerve – a bundle of axons
carrying signals from the spinal
cord to the muscle.
 Within the muscle, each axon
will go its own way and eventu-
ally branch into multiple small
extensions called telodendria.
Each telodendrium 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.
61
Excitation:The Neuromuscular Junction(NMJ)
The minute space between the synaptic end bulb and
the sarcolemma is known as the synaptic cleft.
There is a depression in the sarcolemma at the synap-
tic cleft known as the motor end plate.
• The synaptic end
bulb is filled with
vesicles that contain
the neurotransmitter,
acetylcholine(ACh).
•The motor end plate
is chock full of
acetylcholine recep-
tors, nicotinic re-
ceptor.
62
Excitation: The Neuromuscular Junction…
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 and bind to the ACh re-
ceptors. These receptors are actually 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!
63
• The endplate potential is localized to the endplate region
and is not propagated.
• Adjacent to the motor end plate, the sarcolemma contains
voltage-gated ion channels.
– In order for these channels to open, the VM must depolar-
ize from its resting value of –90 mV to approximately –
50 mV. This is the threshold.
• VM must become this positive for the voltage-gated channels to

open.
• The degree of depolarization depends on how much Na+ influx oc-

curred w/c in turn depends on how many Na+ channels were opened64
• If the VM fails to depolarize to threshold, nothing will happen.
• The VM will soon return to normal & no muscle contraction will oc-
cur.
• If the VM does reach threshold, 2 types of voltage-gated ion channels

will open:
– Fast Na+ channels
– Slow K+ channels
65
• If VM reaches threshold, fast Na+ channels open & Na+ rushes in
causing the VM to depolarize to +30 mV. The depolarization stops
when the Na+ channels become inactivated.
• At this point, slow K+ channels will open & K+ efflux occurs.
This returns VM to its resting level. This is repolarization.
This is known as an action potential.
66
• An AP can propagate itself across the surface of the PM.
• The depolarization caused by the Na+ influx in one particular area
of the sarcolemma causes voltage-gated channels in the adjacent
membrane to open.
• The resulting ionic influx then
causes voltage-gated channels to
open in the next patch of
membrane and so on & so on.
 Thus. AP propagates itself.
67
Characteristics of NMJ
 Transmission is unidirectional
 There is a single NMJ per muscle fiber
 The NT is always Ach
Synthesis: Choline + Acetyl-CoA = ACh by the action of
choline acetyltransferase
Storage: Ach form a complex with ATP, packed in vesicles
Release: Released by Calcium-dependent exocytosis
Metabolism: Metabolized by the action of acetylcholinesterase
 The post-junctional receptor is always nicotinic receptor (NR)
 The effect of Ach on NR is always excitatory producing EPSP/EPP
 There is a synaptic delay (0.2 – 03 ms)
 It is fatigable due to depletion of ATP & NT storage
68
Summary of NMJ activity
 Arrival of AP at axon terminal
 Fusion of synaptic vesicles
 Release of Ach
 Ach binds to its own receptor sites
 Breakdown of Ach by acetylcholinesterase
 AP propagation
 Calcium release from sarcoplasmic reticulum
 Contraction of the muscle cell
69
Drugs that Enhance or Block Transmis-
sion at the NMJ
Drugs that stimulate the muscle fiber by Ach like action
Many compounds, including methacholine, carbachol & nicotine have

the same effect on the muscle fiber as does Ach.
The difference between these drugs and Ach is that, the drugs are not
destroyed by cholinesterase or destroyed so slowly that their action of-

ten persists for many minutes to several hours.
70
sion at the NMJ…
Drugs that stimulate the NMJ by Inactivating Acetyl-

cholinesterase
Particularly three well known drugs:- neostigmine, physostigmine, &
diisopropyl fluorophosphate, inactivate the acetylcholinesterase at the

synapse, so that no longer hydrolyzes acetylcholine.
71
sion at the NMJ…
 The complex series of events making up neuromuscular trans-
mission is subject to interference at several steps.
1. Presynaptic blockade of the NMJ
– Can occur if Ca2+ does not enter the presynaptic terminal to
participate in migration and emptying of the synaptic vesicles.
a. The drug hemicholinium interferes with choline uptake by the
presynaptic terminal and thus, results in the depletion of ACh.
b. Botulinum toxin interferes with Ach release.
– Toxin produced by the bacterium Clostridium botulinum.
72
Drugs that Enhance or Block
Transmission at the NMJ…
 Botulinum toxin is an enzyme that breaks down a protein re-
quired for the binding & fusion of Ach vesicles with the
plasma membrane of the axon terminal.
Blocks the release of Ach from nerve terminals.
 Produces the food poisoning called botulism
 Cause muscle paralysis & asphyxiation
73
2. Postsynaptic blockade
 Can result from a variety of circumstances:
– Drugs that partially mimic the action of Ach can be effective
blockers.
– Curare bind tightly to Ach receptors.
Does not open their ion channels
–Does not destroyed by AchE.

 When a receptor is occupied by curare, ACh cannot bind to the re-
ceptor.
 As a result, there is no AP in the motor end plate & hence no con-
traction.
74
sion at the NMJ…
 Causes loss of voluntary muscular action through paralysis and,
usually, death through arrest of the muscles of respiration
 Medical use
• Muscle relaxants during surgical operations

Reduces the required dose of general anesthetic, allow-
ing patients to recover faster with fewer complications.
• In therapy for diseases such as rabies & tetanus
75
• The drug succinylcholine
– Blocks the NMJ in a slightly different way; this molecule binds
to the receptors and causes the channels to open.
– B/se it is slowly hydrolyzed by AChE, its action is long lasting &
the channels remain open.
– This prevents resetting of the inactivation gates of muscle mem-
brane sodium channels near the endplate region and blocks sub-
sequent action potentials.
– Drugs that produce extremely long-lasting endplate potentials are
referred to as depolarizing blockers.
76
Drugs that Enhance or Block Transmission at
the NMJ…
Organophosphates
Main ingredients in certain pesticides & “nerve gases”
Inhibits acetylcholinesterase
 The Ach is not destroyed,
The motor end plate remain depolarized
 A skeletal-muscle membrane cannot generate APs
 Thus, the muscle does not contract in response to subsequent

nerve stimulation,
Results in skeletal-muscle paralysis & death from asphyxiation.

77
Mechanism of Muscle Contraction
(Excitation-contraction coupling)
When a muscle fibre membrane is depolarized, contrac-
tion of the fibre follows. The process by which de-
polarization 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 synaptic end bulb.
2. Opening of Voltage gated Calcium-channels and
influx of Ca2+ to trigger the release of Ach.
3. ACh released by Calcium-dependent exocytosis
and diffuse through the synaptic cleft and binds to
Nicotinic receptor on postjunctional membrane.
4. Opening of ligand gated Na-channels and influx
of Na+ to produce EPSP.
5. Spread of depolarization through the sarcolemma
6. Spread of depolarization through the T-tubules
78
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 tropomy-
ocin, 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
and then detached from actin leading to relaxation.
79
A Review of Muscle Contraction
80
Contraction Cycle
 Is the repeating sequence of events that causes the filaments to
slide over one another.
 At the onset of contraction, the sarcoplasmic reticulum re-
leases Ca2+ into the cytosol, there, they bind to troponin.
 Troponin then moves tropomyosin away from the myosin

binding sites (active sites) on actin.
 Once the myosin binding sites are “free”, the contraction cycle
begins.
81
Contraction Cycle…
The contraction cycle consists of four steps:

1. ATP hydrolysis
Energizes the myosin head.
2. Attachment of myosin to actin to form crossbridges
Energized myosin head attaches to the active site on actin.
3. Power stroke
Generates force toward the center of the sarcomere, sliding
thin filament past over thick filament toward M line.
4. Detachment of myosin from actin
As ATP binds to the myosin head, the myosin head detaches
from actin.
82
Contraction Cycle…
83
Mechanism of Muscle Relaxation
It has the following steps
1. Following muscle contraction, Ca2+ is re-uptaken back into SR
by Calcium-pump, this requires ATP.
2. Decreased Ca2+ in the sarcoplasm→ Ca2+ detaches from tro-
ponin-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
84
Rigor Mortis
After death, cellular membranes become leaky. Calcium
ions leak out of the sarcoplasmic reticulum into the cytosol
and allow myosin heads to bind to actin.
ATP synthesis ceases shortly after breathing stops, however,
so the crossbridges cannot detach from actin. The resulting
condition, in which muscles are in a state of rigidity (cannot
contract or stretch), is called rigor mortis (rigidity of
death).
Rigor mortis begins 3–4 hours after death and lasts about 24
hours; then it disappears as proteolytic enzymes from lyso-
somes digest the crossbridges.
85
Types of Muscle Contractions
1. Isometric contraction (constant length)
• Iso = same; metr = length
 When a muscle develops tension but does not shorten or
lengthen, the contraction is said to be an isometric (constant
length) contraction.
 The tension generated is not enough to exceed the resistance of
the object to be moved, the muscle does not change its length.
 Such contractions occur when the muscle supports a load in a
constant position or attempts to move an otherwise supported
load that is greater than the tension developed by the muscle.
 An example would be holding a book steady using an out-
stretched arm
86
Types of Muscle Contractions…
• It is the type of contraction with no change in length
• No work is done in this type of contraction
87
2. Isotonic contraction (constant tension)
– Iso=same, ton=tension
 Tension developed by the muscle remains almost constant while
the muscle changes its length.
 Isotonic contractions are used for body movements and for moving
objects.
 The two types of isotonic contractions are concentric and eccentric.
 In a concentric isotonic contraction, if the tension generated is
great enough to overcome the resistance of the object to be moved,
the muscle shortens.
 Picking a book up off a table involves concentric isotonic contractions.
 Eccentric isotonic contraction, when the length of a muscle in-
creases during a contraction.
 As you lower the book to place it back on the table, the previously shortened bi-
ceps lengthens in a controlled manner while it continues to contract 88
• It is the type of contraction with no change in muscle tension
• Occurs when contraction moves an object of moderate weight
• Work is done in this type of contraction
Concentric Isotonic Eccentric Isotonic

Contraction Contraction
89
Force of Skeletal Muscle Contraction
 Determined by:
1. Number of motor units activated
2. Size of muscle
– increasing the size of individual muscle cells (not increasing cell #)
3. Series-elastic elements
– sheath around the muscle & the connective tissue tendons that attach
muscle to bone
– "stretching" of non-contractile parts allows time for muscle to produce a
tetanic contraction
4. Degree of muscle stretch (actin-myosin overlap)
90
Muscle Metabolism
Muscle fibers have three ways to produce ATP:

1. From creatine phosphate
2. By anaerobic cellular respiration and
3. By aerobic cellular respiration
 The use of creatine phosphate for ATP production is unique

to muscle fibers, but all body cells make ATP by the reac-
tions of anaerobic and aerobic cellular respiration.
91
Muscle Metabolism…
1. Creatine Phosphate
 While muscle fibers are relaxed, they produce more ATP than
they need for resting metabolism.
 The excess ATP is used to synthesize creatine phosphate, an en-
ergy-rich molecule that is found only in muscle fibers.
 The enzyme creatine kinase (CK) catalyzes the transfer of one of
the high-energy phosphate groups from ATP to creatine, forming
creatine phosphate and ADP.
 Creatine phosphate and ATP provide enough energy for muscles
to contract maximally for about 15 seconds.
92
93
2. Anaerobic Cellular Respiration
 Anaerobic cellular respiration is a series of ATP-producing reac-
tions that do not require oxygen.
 When muscle activity continues and the supply of creatine phos-
phate within the muscle fiber is depleted, glucose is catabolized to
generate ATP.
 Anaerobic cellular respiration can provide enough energy for about
30 to 40 seconds of maximal muscle activity.
94
1. Large amounts of glucose are

used for very small ATP re-
turns.
2. Lactic acid is a toxic end
product whose presence con-
tributes to muscle fatigue.
• Dominates in sports that requires

bursts of speed & activity
e.g. Basketball.
95
3. Aerobic Cellular Respiration
 Muscular activity that lasts longer than half a minute depends in-
creasingly on aerobic cellular respiration, a series of oxygen-re-
quiring reactions that produce ATP in mitochondria.
 Muscle tissue has two sources of oxygen:
1. Oxygen that diffuses into muscle fibers from the blood and
2. Oxygen released by myoglobin within muscle fibers.
 Both myoglobin (found only in muscle cells) and hemoglobin
(found only in red blood cells) are oxygen-binding proteins.
 Aerobic cellular respiration supplies enough ATP for prolonged
activity provided sufficient oxygen and nutrients are available.
96
 It occurs in the mitochondria.
 Pyruvic acid from glycolysis is
the primary substrate.
 The cell also utilizes fatty acids &
amino acids.
 Aerobic respiration typically
yields 36 ATP per molecule of
glucose.
97
98
Types of Skeletal Muscle Fibers
 Skeletal muscle fibers are not all alike in composition and
function.
 Vary in their diameter, myoglobin content, metabolic reac-

tions, ATPase activity, speed of contraction and relaxation and
in how quickly they fatigue.
 Fibers with a high myoglobin content are termed red muscle

fibers and appear darker; those with a low content of myo-
globin are called white muscle fibers and appear lighter.
99
Types of Skeletal Muscle Fibers…
 Red muscle fibers also contain more mitochondria and sup-

plied by more blood capillaries.
 Based on all these structural and functional characteristics,

skeletal muscle fibers are classified into three main types:
1. Slow oxidative fibers (type I)
2. Fast oxidative-glycolytic fibers (type IIa)
3. Fast glycolytic fibers (type IIb)
100
1. Slow-oxidative (SO) fibers or red fibers
 Small in diameter and appear dark red because they contain a

large amount of myoglobin and many blood capillaries.
 Have many large mitochondria and generate ATP mainly by

aerobic cellular respiration.
 “Slow” because the contraction cycle proceeds at a slower

pace than in “fast” fibers.
 Are very resistant to fatigue and are capable of prolonged,

sustained contractions. 101
2. Fast oxidative-glycolytic (FOG) fibers
 Intermediate in diameter and contain a large amount of myo-

globin, and thus appear dark red.
 Generate considerable ATP by aerobic cellular respiration,

which gives them a moderately high resistance to fatigue.
 They also generate ATP by anaerobic glycolysis.
 “Fast” because they contract and relax more quickly than slow
oxidative fibers.
102
3. Fast-glycolytic (FG) fibers or white fibers

 Are largest in diameter contain the most myofibrils, and gen-
erate the most powerful and rapid contractions.
 They have low myoglobin content and few mitochondria.
 Contain large amounts of glycogen and generate ATP mainly

by anaerobic glycolysis.
 They are used for intense movements of short duration, but

they fatigue quickly.
103
104
Muscle Hypertrophy and Atrophy
 When the total mass of a muscle increases (hypertrophy) and

decreases (atrophy).
 Virtually all muscle hypertrophy results from an increase in

the number of actin and myosin filaments in each muscle fiber.
 Hypertrophy occurs to a much greater extent when the muscle

is loaded during the contractile process.
105
Muscle Hypertrophy and Atrophy…
 The manner in which forceful contraction leads to hypertrophy
is not known.
 However, that the rate of synthesis of muscle contractile pro-
teins is far greater during hypertrophy.
 Along with the increasing size of myofibrils, the enzyme sys-
tems that provide energy increase, number of mitochondria,
myoglobin, sarcomeres.
 When a muscle remains unused , the rate of decay of the con-
tractile proteins is greater than the rate of replacement.
 Therefore, muscle atrophy occurs
106
Muscle Hypertrophy and Atrophy…
 Muscle atrophy: Disuse atrophy &
Denervation atrophy
 Muscle hypertrophy: Increase in size of muscle fiber
 Changes:
 ↑№ of actin and myosin filaments in each fiber
 ↑№ of sarcomeres
 ↑Enzyme system of glycolysis
 ↑Amount of myoglobin, ↑Mitochondria
 ↑№ of capillaries
 As a result, there is an increase in the force and strength of
contraction, decrease in fatigability
107
Muscle Fatigue
 Physiological inability to respond to a stimulus.
 Temporary inability of an organ /body part (muscle/nerve cell)

to respond to a stimulus & function normally after continuous
activity/stimulation.
 Results primarily from a relative deficit of ATP.
108
Muscle Fatigue…
 When a skeletal-muscle fiber is repeatedly stimulated, the ten-
sion developed by the fiber eventually decreases even though
the stimulation continues.
 This decline in muscle tension as a result of previous contrac-

tile activity is known as muscle fatigue.
 The inability of a muscle to contract forcefully after prolonged

activity is called muscle fatigue.
109
Muscle Fatigue…
 One important factor in muscle fatigue is lowered release of

calcium ions from the sarcoplasmic reticulum.
 Other factors that contribute to muscle fatigue include deple-

tion of creatine phosphate, insufficient oxygen, depletion of
glycogen and other nutrients.
110
Muscle Fatigue…
 If a muscle is allowed to rest after the onset of fatigue, it can
recover its ability to contract upon re-stimulation.
 The rate of recovery depends upon

The duration & intensity of the previous activity.
 Some muscle fibers fatigue rapidly if continuously stimulated

but also recover rapidly after a brief rest.
This is the type of fatigue (high-frequency fatigue) that ac-
companies high-intensity, short-duration exercise, such as
weight lifting.
111
Muscle Fatigue…
• In contrast, low-frequency fatigue develops more slowly with
low-intensity, long-duration exercise, such as long-distance run-
ning, during which there are cyclical periods of contraction & re-
laxation.
– This type of fatigue requires much longer periods of rest, often
up to 24 h, before the muscle achieves complete recovery.
• Muscle fatigue may have function as a mechanism for preventing

the onset of rigor.
112
Muscle Fatigue…
 Many factors can contribute to the fatigue of skeletal muscle.
 Fatigue from high-intensity, short duration exercise is thought to
involve at least three different mechanisms:
1. Conduction failure
The muscle AP can fail to be conducted into the fiber along the
T-tubules, w/c terminates the release of Ca2+ from the SR.
2. Lactic acid buildup
o Alters a № of muscle proteins, including
Actin & myosin;
Proteins involved in Ca2+ release.
Ca2+-ATPase pump
 Impaired relaxation of fatigued muscle.
113
Muscle Fatigue…
3. Inhibition of cross-bridge cycling
Due to buildup of ADP & Pi within muscle fibers
Delays cross-bridge detachment from actin
Changes contribute to the reduced shortening velocity & im-
paired relaxation
Resulting from high-intensity exercise.
114
Just compare who is better at…
Muscle Size
Speed
Power
Endurance
 Fatigue
115
Cardiac Muscle
 Is muscle of the heart.
 Striated and has a sarcomere.
 Has a single nucleus.
 Shorter than skeletal muscle fibers, may be branched.
 Involuntary, controlled by autonomic nervous system, drugs
and hormones.
 Has the property of autorhythmicity and syncytium.
 Extensively connected by gap junctions, through which action
potential travels the entire cell network.
116
Cardiac Muscle…
 Cardiac muscle fibers have the same arrangement of actin and
myosin and the same bands, zones, and Z discs as skeletal muscle
fibers.
 However, intercalated discs are unique to cardiac muscle fibers.
The discs contain desmosomes, which hold the fibers together, and
gap junctions, which allow muscle action potentials to spread from
one cardiac muscle fiber to another.
 Cardiac muscle tissue has an endomysium and perimysium, but
lacks an epimysium.
 In response to a single action potential, cardiac muscle tissue re-
mains contracted 10 to 15 times longer than skeletal muscle tissue.
The long contraction is due to prolonged delivery of Ca2+ into the
sarcoplasm.
117
Cardiac Muscle…
 Cardiac muscle tissue contracts when stimulated by its own au-
torhythmic muscle fibers but skeletal muscle tissue contracts only
when stimulated by acetylcholine released by a nerve impulse in a
motor neuron.
 The mitochondria in cardiac muscle fibers are larger and more
numerous than in skeletal muscle fibers.
118
Cardiac Muscle…
119
Cardiac Muscle…
Basic organization of cardiac muscle cells
 Cardiac muscle cells are much smaller than skeletal muscle
cells.
 Typically, cardiac muscle cells measure 10μm in diameter and

approximately 100μm in length.
 Cardiac cells are connected to each other through intercalated

disks (include both mechanical and electrical connections).
 The mechanical connections keep the cells from pulling apart

when contracting.
120
Cardiac Muscle…
 Electrical connections (gap junctions) allow propagation of ac-
tion potential throughout the heart.
 Thus, the arrangement of cardiac muscle cells is said to form

an electrical and mechanical syncytium.
 Single action potential (generated within the sinoatrial node)

pass throughout the heart so that the heart can contract in a
synchronous, wave-like fashion.
121
Cardiac Muscle…
122
Cardiac Muscle…
Control of cardiac muscle activity

 Cardiac muscle is an involuntary muscle with an intrinsic
pacemaker.
 The pacemaker represents a specialized cell located in the

right atrium (sinoatrial node) that is able to undergo sponta-
neous depolarization and generate action potentials.
 Depolarization from only one cell is needed to initiate a wave

of contraction in the heart (i.e. heartbeat).
123
Cardiac Muscle…
Excitation-contraction coupling
 Action potential in cardiac muscle lasting 150-300msec longer
than the action potentials in skeletal muscle (≈5msec).
 The long action potential duration in cardiac muscle is due to a

slow inward Ca2+ current through a voltage-gated L-type Ca2+
channel in the sarcolemma.
 Thus, influx of Ca2+ during the action potential is critical for

triggering release of Ca2+ from the SR and thus initiating con-
traction.
124
Cardiac Muscle…
1. Depolarization of the plasma membrane causes voltage-gated
Ca2+ channels to open in the T-tubules.
2. This allows some Ca2+ to diffuse from the ECF into the cyto-
plasm, which stimulates the opening of Ca2+ release channels
in the SR.
3. The Ca2+ released from the SR binds to troponin and stimulates

contraction.
4. Ca2+ pump actively transports Ca2+ into the cisternae of the

SR, allowing relaxation of the myocardium. 125
Cardiac Muscle…
126
Cardiac Muscle…
 The heart is composed of three major types of cardiac muscle:
1. Atrial muscle
2. Ventricular muscle, and
3. Specialized excitatory & conductive muscle fibers.
 The atrial & ventricular types of muscle contract in much the

same way as skeletal muscle, except that the duration of con-
traction is much longer.
127
Smooth Muscle
Located in the wall of hallow organs (gastrointestinal tract,

blood vessels, uterus, urinary bladder).
They have non-striated appearance, mono-nucleated cells.
Involuntary muscle, controlled by autonomic nervous sys-

tem, drugs and hormones.
Have the property of autorhythmicity and syncytium.
128
Smooth Muscle…
 Smooth muscle cells do not receive direct synaptic connec-
tions to specific cells.
 Neurotransmitter is released from varicosities (swellings) lo-

cated at intervals along the axon and diffuses over a relatively
long distance to large groups of cells.
 Consequently, neighboring muscle cells tend to contract or re-

lax together.
129
Smooth Muscle…
130
Smooth Muscle…
Types of smooth muscle
 The smooth muscle of each organ is distinctive from that of
most other organs in several ways:
 Organization into bundles or sheets,
 Response to different types of stimuli,
 Characteristics of innervation, and function.
 Generally smooth muscle can be divided into two major types:

multi-unit and single-unit (unitary) smooth muscle.
131
Smooth Muscle…
Visceral (single-unit) Multiunit smooth muscle
smooth muscle
 More common type Less common type
 Found in small arteries ,small Found in the walls of large ar-
veins, stomach, intestines, teries, in airways to the lungs,
uterus, and urinary bladder. in the arrector pili
 Autorhythmic muscles that attach to hair fol-
licles.
 The fibers connect to one an-
Lack gap junctions
other by gap junctions, through
which muscle action potentials Stimulation of one multiunit
can spread fiber causes contraction of that
fiber only.
132
Smooth Muscle…
 Smooth muscle tissue exhibits some important physiological
differences from cardiac and skeletal muscle tissue.
 Contraction in a smooth muscle fiber starts more slowly and

lasts much longer than skeletal muscle fiber contraction.
 Another difference is that smooth muscle can both shorten and

stretch to a greater extent than the other muscle types.
133
Smooth Muscle…
Unitary smooth muscle

 The term “unitary“ does not mean single muscle fibers, in-
stead, it means a mass of hundreds to thousands of smooth
muscle fibers that contract together as a single unit.
 The fibers are arranged in sheets or bundles, and their cell

membranes are adherent to one another at multiple points.
 Force generated in one muscle fiber can be transmitted to the

next.
134
Smooth Muscle…
 Are electrically coupled such that electrical stimulation of one
cell is followed by stimulation of adjacent smooth muscle
cells.
 Are also called syncytial smooth muscle or visceral smooth

muscle because muscle fibers connect to one another by gap
junctions.
 Found in the walls of most viscera of the body, the GIT, bile
ducts, ureters, uterus, and blood vessels.
135
Smooth Muscle…
Multi-unit smooth muscle

 Composed of discrete, separate smooth muscle fibers, each
operates independently of the others and often innervated by a
single nerve ending.
 Each fiber can contract independently of the others, stimula-

tion of one multiunit fiber causes contraction of that fiber only.
 Found in the walls of large arteries, in airways, ciliary and iris

muscle of the eye, piloerector muscles that cause erection of
the hairs.
136
Smooth Muscle…
137
Smooth Muscle…
Microscopic anatomy of smooth muscle

 A single relaxed smooth muscle fiber is 30–200µm long and it
is thickest in the middle (3–8µm) and tapers at each end.
 Within each fiber is a single, oval, centrally located nucleus

and the sarcoplasm contains both thick filaments and thin fil-
aments, in ratios between 1:10 and 1:15.
 Thick filaments and thin filaments are not arranged in orderly

sarcomeres.
138
Smooth Muscle…
 Various filaments have no regular pattern of overlap, i.e. they
do not exhibit striations.
 Smooth muscle fibers also lack transverse tubules and have

only a small amount of SR for storage of Ca2+.
 Thin filaments attach to structures called dense bodies, which

are functionally similar to Z discs in striated muscle fibers.
 Some dense bodies are dispersed throughout the sarcoplasm,

others are attached to the sarcolemma.
139
Smooth Muscle…
140
Smooth Muscle…
 Smooth muscle fibers have thick and thin filaments but no
T-tubules and scanty SR.
141
Smooth Muscle…
Membrane potentials in smooth muscle

 Many types of smooth muscle display unstable resting mem-
brane potentials that vary between -40 and -80 mV.
 Cells that exhibit cyclic depolarization and repolarization of

their membrane potential are said to have slow wave poten-
tials.
 The cell simply cycles through a series of sub-threshold slow

waves, however, if the peak of the depolarization reaches
threshold, action potentials fire.
142
Smooth Muscle…
Action potentials in smooth muscle

 The smooth muscle cell membrane has far more voltage-gated
calcium channels than does skeletal muscle but few voltage-
gated sodium channels.
 Calcium channels are responsible for generating the smooth

muscle action potential.
 Flow of calcium ions to the interior of the fiber is mainly re-

sponsible for the action potential.
143
Smooth Muscle…
 However, the calcium

channels open more slowly
than do sodium channels,
and they also remain open
much longer.
 This accounts for the pro-

longed plateau action po-
tentials of some smooth
muscle fibers.
144
Smooth Muscle…
Contraction of smooth muscle

 Starts more slowly and lasts much longer than skeletal muscle
fiber.
 Smooth muscle can both shorten and stretch to a greater ex-
tent than the other muscle types.
 An increase in the concentration of Ca2+ in the cytosol initiates

contraction, just as in striated muscle.
145
Smooth Muscle…
 Calcium ions flow into smooth muscle cytosol from both the
interstitial fluid and SR (few).
 Calmodulin binds to Ca2+ in the cytosol and activates an en-

zyme called myosin light chain kinase, which adds a phos-
phate group to myosin head.
 Once the phosphate group is attached, the myosin head can

bind to actin because phosphorylation of myosin enhances
myosin ATPase activity and results in contraction.
146
Smooth Muscle…
 Source of calcium ions for smooth muscle contraction is cal-
cium ions that diffuse into muscle fiber at the time of the ac-
tion potential from ECF.
 Therefore, the force of contraction of smooth muscle is usu-

ally highly dependent on ECF calcium ion concentration.
147
Smooth Muscle…
148
Smooth Muscle…
149
Smooth Muscle…
 Most smooth muscle fibers contract or relax in response to ac-
tion potentials from the autonomic nervous system.
 In addition, many smooth muscle fibers contract or relax in re-

sponse to:
 Stretching
 Hormones, or
 Local factors such as changes in pH, oxygen and carbon
dioxide levels, temperature, and ion concentrations.
150
Smooth Muscle…
Regulation of smooth muscle contraction

 Smooth muscle cells undergo changes in membrane potential
in response to neural, hormonal, or mechanical stimulation.
 Many smooth muscle cells are capable of initiating sponta-

neous electrical activity and others can contract without action
potentials.
 Some smooth muscle cells can also contract without any

change in membrane potential.
151
Smooth Muscle…
 Smooth muscle contraction is controlled by hormones and
paracrines in addition to neurotransmitters.
 Two types of non-nervous and non-action potential stimulating

factors often involved are:
1. Local tissue chemical factors
Level of O2 , CO2 , H+, adenosine, lactic acid, K+ , Ca++ body temper-
ature etc.
2. Various hormones
Norepinephrine, epinephrine, angiotensin, endothelin, vasopressin,
oxytocin, serotonin, histamine etc.
152
Smooth Muscle…
153
Thank You!
154

Physiology U-4 Excitable Muscle Tissue

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Physiology U-4 Excitable Muscle Tissue

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Excitable Tissue: Muscu-

 Specifically, muscle cells use the energy in ATP to generate force or

Located attached to bones & moves skeleton.

Thermogenesis (Heat production)

 Generation of heat. Occurs via shivering – an involuntary con-

 The term muscle refers to a number of muscle fibers bound to-

 The relationship between a single muscle fiber and a muscle is

 Muscle fibers contains several hundreds to thousands of myofibrils

 The diameter of a mature skeletal muscle fiber ranges from 10

 The typical length of a mature skeletal muscle fiber is 10 cm.

 Each mature skeletal muscle fiber has a hundreds or more nu-

 Thousands of tiny invaginations of the sarcolemma, called

 Muscle action potentials travel along the sarcolemma and

Structures of skeletal muscle cell

 Surrounds myofibrils and

 Its function is to store cal-

 Are about 2µm in diameter and extend the entire length of a

 Each muscle fiber contains several hundred to several thou-

 Each myofibril is made up 1000’s of repeating basic functional

 Each sarcomere is an ordered arrangement of thick (myosin)

 Sarcoplasmic reticulum wraps around each myofibril.

Thin myofila- Thick myofila-

 Two types of myofilaments which make up myofibrils:

• Actin Contractile Pro-

Each thin filament consists of a long helical double strand. This

Bound to both actin & tropomyosin, there is a trio of proteins col-

 They are complex of three loosely bound protein sub-units

 This complex is believed to attach the tropomyosin to actin

The basic components of each thin filament are actin

G-actins are linked together end to end, like pearls in a neck-

Two F-actins are arranged in a double helix to form the actin

 Thin filaments contain two regulatory proteins that enable

and “drags” tropomyosin off the myosin binding sites on actin.

 A single myosin protein

wide, dark band known as the A-band.

 Because the middle of the thick filament is devoid of cross-

 Each myosin molecule is a dimer consisting of two inter-

 The heads of myosin molecules are called “crossbridges” be-

 The head is the “business end” of the myosin molecule—it is

Characteristics of the Myosin Head:

Characteristics of the Myosin Head:

 These striations are due to the orderly arrangement of protein

 The thin and thick filaments exist in a 2:1 ratio.

 The Z disc is composed of filamentous proteins different from

 The Z disc proteins pass crosswise across the myofibril and

 M-line is the middle of the H zone and functions to hold the

 The portion of the sarcomere which contains the thick filament

 H zone contains only thick filaments.

This pulls the Z-discs close together.

shorter which pulls on the endomysium, perimysium, epimy-

Here is what happens

• The site of interaction b/n a neuron and any other cell

• VM must become this positive for the voltage-gated channels to

• The degree of depolarization depends on how much Na+ influx oc-

• If the VM fails to depolarize to threshold, nothing will happen.

• If the VM does reach threshold, 2 types of voltage-gated ion channels

Many compounds, including methacholine, carbachol & nicotine have

destroyed by cholinesterase or destroyed so slowly that their action of-

Drugs that stimulate the NMJ by Inactivating Acetyl-

Particularly three well known drugs:- neostigmine, physostigmine, &

diisopropyl fluorophosphate, inactivate the acetylcholinesterase at the

 Produces the food poisoning called botulism

 Cause muscle paralysis & asphyxiation

–Does not destroyed by AchE.