Chapter 8 - Muscle Physiology

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1

BIO2305



Muscle Physiology




Muscle accounts for nearly half of the body’s mass
-

Muscles have the ability to change
chemical energy (ATP) into mechanical energy



Three types of Muscle Tissue


differ in structure, location, function, and means of activati
on

1.

Skeletal Muscle

2.

Cardiac Muscle
-

forms most of the heart, it is striated, involuntary, autorhythmic

3.

Smooth Muscle
-

located in the walls of hollow internal structures, nonstriated,
involuntary



Skeletal
Muscle



Skeletal muscles attach to and cover the bo
ny skeleton



Is controlled voluntarily (i.e., by conscious control)



Contracts rapidly but tires easily



Is responsible for overall body motility



Is extremely adaptable and can exert forces ranging from a fraction of an ounce to over 70
pounds



Has obvious str
ipes called striations



Each muscle cell is multinucleated


2


Sarcolemma



A

muscle fiber plasma (cell) membrane


Sarcoplasm



M
uscle fiber cytoplasm, almost completely filled with contractile filaments called
myofilaments

(thick, thin & elastic)



Sarcoplasm con
tains glycosomes (granules of glycogen) and the oxygen
-
binding protein called
myoglobin



In addition to the typical organelles, fibers have

o

Sarcoplasmic reticulum

o

T tubules
-

modifications of the sarcolemma

o

Myofibrils



Each muscle fiber is made of many myof
ibrils, 80% of the muscle volume, that contain the
contractile elements of skeletal muscle cells






3

Myofibrils


Striations



Myofibrils are made up of 2 types of contractile proteins called myofilaments



Thick (Myosin) filaments



Thin (Actin) filaments



T
he arrangement of myofibrils creates a series of repeating dark
A (anisotropic) bands

and
light
I (isotropic) bands






The A band has a light stripe in the center called the H (helle) zone



The H zone is bisected by a dark line, the M line



I band has a d
arker midline called the Z disc (or Z line)



Sarcomere



Smallest contractile unit of a muscle



Myofibril region between two successive Z discs, has a central A band and partial (half) I bands
at each end



C
haracterized by alternating light and dark bands or

zones produced by the myofilaments



Z disc

-

a line that separates one sarcomere from another



M line

-

central line of the sarcomere where myosin filaments are anchored



H zone

-

the area where only myosin filaments
are present




I band

-

the area where onl
y actin filaments are present



A band

-

includes overlapping myosin and actin filaments



4



Thick Filaments (16 nm diam) Myosin



Each myosin molecule (two interwoven polypeptide chains) has a rod
-
like tail and two globular
heads



During muscle contraction, th
e h
eads link the thick and thin filaments together, forming cross
bridges


Thin Filaments
-

Actin



Thin filaments are mostly composed of the protein actin.



Provides active sites where myosin heads attach during contraction.
Tropomyosin

and
Troponin

are
regulatory subunits bound to actin.




5

Ultrastructure of Muscle

Myofibril
A band
Z disk
Z disk
Z disk
I band
M line
H zone
Z disk
Sarcomere
Thin filaments
Tropomyosin
Troponin
Actin
chain
G
-
actin
molecule
Myosin tail
Myosin
heads
Myosin molecule
(c)
(d)
(e)
Thick filaments
Hinge
region
(f)
Titin
Nebulin
Titin
M line
M line
Myofibril
A band
Z disk
Z disk
Z disk
I band
M line
H zone
Z disk
Sarcomere
Thin filaments
Tropomyosin
Troponin
Actin
chain
G
-
actin
molecule
Myosin tail
Myosin
heads
Myosin molecule
(c)
(d)
(e)
Thick filaments
Hinge
region
(f)
Titin
Nebulin
Titin
M line
M line

Arrangement of Filaments in a Sarcomere



Sarcoplasmic reticulum

(endoplasmic reticulum)



A

network of tubes surrounding myofibrils, functions to reabsorb calcium ion during
relaxation, re
lease them to cause contraction.


6



SR
-

an elaborate, smooth ER that surrounds each myofibril. Perpendicular (transverse)
channels at the A band
-

I band junction are the
Terminal Cisternae
(Lateral Sacs) SR
regulates
intracellular Ca2+



T tubules at each A
band/I band junction
-

continuous with the sarcolemma. Conduct electrical
impulses to the throughout cell (every sarcomere)
-

signals for the release of Ca2+ from
adjacent terminal cisternae




Transverse tubules




Tubules formed by invaginations of the sa
rcolemma and flanked by the sarcoplasmic reticulum



They carry action potentials deep into the muscle fiber.



T tubules and SR provide tightly linked signals for muscle contraction.



Triad


2 terminal cisternae and 1 T tubule



T tubules and SR provide ti
ghtly linked signals for muscle contraction



Interaction of integral membrane proteins (IMPs) from T tubules and SR


7



Interaction of T
-
Tubule Proteins and SR Foot Proteins



T tubule proteins (Dihydropyridine) act as voltage sensors



SR foot proteins are (r
yanodine) receptors that regulate Ca2+ release from the SR cisternae



Action potential in t
-
tubule alters conformation of DHP receptor



DHP receptor opens Ca2+ release channels in sarcoplasmic reticulum and Ca2+ enters
cytoplasm

Ca
2+
Ca
2+
released
(b)
DHP receptor
SR Foot Protein (Ca++ release channel)
Ca
2+
Ca
2+
released
(b)
DHP receptor
SR Foot Protein (Ca++ release channel)









Sliding Filament Mo
del of Contraction



Contraction refers to the activation of myosin’s cross bridges


the sites that generate the force


8



In the relaxed state, actin and myosin filaments do not fully overlap



With stimulation by the nervous system, myosin heads bind to actin a
nd pull the thin filaments



Actin filaments slide past the myosin filaments so that the actin and myosin filaments overlap
to a greater degree (the actin filaments are moved toward the center of the sarcomere, Z lines
become closer)



Skeletal Muscle Cont
raction



For contraction to occur, a skeletal muscle must:



Be stimulated by a nerve ending



Propagate an electrical current, or
action potential
,

along its sarcolemma



Have a rise in intracellular Ca2+ levels, the final stimulus for contraction



The series of
events linking the action potential to contraction is called
excitation
-
contraction
coupling



Individual muscle fibers contract to their fullest extent; they do not partially contract, this
follows the
all or none principle.



Depolarization and Generation
of an AP



The sarcolemma, like other plasma membranes is polarized. There is a
potential difference

(voltage) across the membrane



When Ach binds to its receptors on the motor end plate, chemically (ligand) gated ion channels
in the receptors open and allo
w Na+ and K+ to move across the membrane, resulting in a
transient change in membrane potential
-

Depolarization




End plate potential

-

a local depolarization that creates and spreads an
action potential

across
the sarcolemma


Excitation
-
Contraction Coupl
ing




E
-
C Coupling is the sequence of events linking the transmission of an action potential along the
sarcolemma to muscle contraction (the sliding of myofilaments)



The action potential lasts only 1
-
2 ms and ends before contraction occurs.



The period bet
ween action potential initiation and the beginning of contraction is called the
latent period
.



E
-
C coupling occurs within the latent period.





9

Regulatory

Role of Tropomyosin and Troponin

P
i
ADP
G
-
actin
moves
Cytosolic
Ca
2+
Tropomyosin
shifts,
exposing binding
site on G
-
actin
TN
Power stroke
Initiation of contraction
Ca
2+
levels increase
in
cytosol
.
Ca
2+
binds to
troponin
.
Troponin
-
Ca
2+
complex pulls
tropomyosin
away from G
-
actin
binding site.
Myosin binds
to
actin
and
completes power
stroke.
Actin
filament
moves.
(b)
1
2
3
4
5
1
2
3
4
5
P
i
ADP
G
-
actin
moves
Cytosolic
Ca
2+
Tropomyosin
shifts,
exposing binding
site on G
-
actin
TN
Power stroke
Initiation of contraction
Ca
2+
levels increase
in
cytosol
.
Ca
2+
binds to
troponin
.
Troponin
-
Ca
2+
complex pulls
tropomyosin
away from G
-
actin
binding site.
Myosin binds
to
actin
and
completes power
stroke.
Actin
filament
moves.
(b)
1
2
3
4
5
1
2
3
4
5



Excitation
-
Contraction Coupling

Muscle fiber
Motor end plate
ACh
Axon terminal of
somatic motor neuron
Sarcoplasmic
reticulum
Actin
Troponin
Tropomyosin
Myosin
head
Z disk
Myosin thick filament
M line
T
-
tubule
DHP
receptor
Ca
2+
Somatic motor neuron
releases
ACh
at
neuro
-
muscular junction.
Net entry of Na
+
through
ACh
receptor
-
channel initiates
a muscle action potential.
Na
+
K
+
(a)
potential
1
Action
2
1
2
Action potential
Muscle fiber
Motor end plate
ACh
Axon terminal of
somatic motor neuron
Sarcoplasmic
reticulum
Actin
Troponin
Tropomyosin
Myosin
head
Z disk
Myosin thick filament
M line
T
-
tubule
DHP
receptor
Ca
2+
Somatic motor neuron
releases
ACh
at
neuro
-
muscular junction.
Net entry of Na
+
through
ACh
receptor
-
channel initiates
a muscle action potential.
Na
+
K
+
(a)
potential
1
Action
2
1
2
Action potential


10


Excitation
-
Contraction Coup
ling



The AP lasts only 1
-
2 ms and ends before contraction occurs. The period between action
potential initiation and the beginning of contraction is called the latent period. E
-
C coupling
occurs within the latent period.



The action potential is propagated

along (across) the sarcolemma and travels through the T
tubules



At the triads, the action potential causes voltage sensitive T tubule proteins to change shape.
This change, in turn, causes the SR foot proteins of the terminal cisternae to change shape,
C
a2+ channels are opened and Ca2+ is released into the sarcoplasm (where the myofilaments
are)

Terminal button
Acetylcholine
-
gated
cation
channel
Acetylcholine
T tubule
Surface membrane of muscle cell
Tropomyosin
Troponin
Cross
-
bridge binding
Myosin cross bridge
Actin
Terminal button
Acetylcholine
-
gated
cation
channel
Acetylcholine
T tubule
Surface membrane of muscle cell
Tropomyosin
Troponin
Cross
-
bridge binding
Myosin cross bridge
Actin



Some of the Ca2+ binds to troponin, troponin changes shape and causes tropomysin to move
which exposes the active binding sites on actin



Myosin heads can now al
ternately attach and detach, pulling the actin filaments toward the
center of the sarcomere (ATP hydrolysis is necessary)



The ATP attached to the myosin head is split by ATPase causing the myosin heads to be
activated.



The activated myosin head attaches to

the actin binding site, then swivels, producing a
power stroke which results in the sliding of the filaments. The ADP and P are released.
Contraction refers to the activation of myosin’s cross bridges


the sites that generate
the force



Onc
e the power st
roke is complete,

ATP again attaches to the myosin head causing the
head to detach from the actin site and return to its original position.



Cycle can then be repeated over and over again as long as calcium and ATP are present.



Relaxation is caused by the b
reaking down of ACh by the enzyme acetylcholinesterase and the
reabsorption of calcium back into the SR



The short calcium influx ends (30 ms after the action potential ends) and Ca2+ levels
fall. An ATP
-
dependent Ca2+ pump is continually moving Ca2+ back
into the SR.



Tropomyosin blockage of the actin binding sites is reestablished as Ca2+ levels drop.
Cross bridge activity ends and relaxation occurs



11



The Molecular Basis of Contraction


12

At the end of the power stroke,
the myosin head releases ADP
and resumes the tightly bound
rigor state.
ATP
binding
site
Myosin
binding
sites
ADP
Tight binding in the rigor
state. The
crossbridge
is
at a 45
°
angle relative to
the filaments.
Myosin filament
45
°
G
-
actin
molecule
ATP binds to its binding site
on the myosin. Myosin then
dissociates from
actin
.
The
ATPase
activity of myosin
hydrolyzes the ATP. ADP and
P
i
remain bound to myosin.
ATP
The myosin head swings over and
binds weakly to a new
actin
molecule.
The
crossbridge
is now at 90
º
relative
to the filaments.
P
i
P
i
ADP
90
°
Release of P
i
initiates the power
stroke. The myosin head rotates
on its hinge, pushing the
actin
filament past it.
P
i
Actin
filament
moves toward M line.
Contraction
-
relaxation
Sliding
filament
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
5
1
2
3
4
5
1
6
2
3
5
4
At the end of the power stroke,
the myosin head releases ADP
and resumes the tightly bound
rigor state.
ATP
binding
site
Myosin
binding
sites
ADP
Tight binding in the rigor
state. The
crossbridge
is
at a 45
°
angle relative to
the filaments.
Myosin filament
45
°
G
-
actin
molecule
ATP binds to its binding site
on the myosin. Myosin then
dissociates from
actin
.
The
ATPase
activity of myosin
hydrolyzes the ATP. ADP and
P
i
remain bound to myosin.
ATP
The myosin head swings over and
binds weakly to a new
actin
molecule.
The
crossbridge
is now at 90
º
relative
to the filaments.
P
i
P
i
ADP
90
°
Release of P
i
initiates the power
stroke. The myosin head rotates
on its hinge, pushing the
actin
filament past it.
P
i
Actin
filament
moves toward M line.
Contraction
-
relaxation
Sliding
filament
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
5
1
2
3
4
5
1
6
2
3
5
4

Sequential Events of Contraction


13



Motor Unit



Motor unit
-

One mo
tor neuron and the muscle fibers it innervates



Number of muscle fibers varies among different motor units



Number of muscle fibers per motor unit and number of motor units per muscle vary widely



Muscles that produce precise, delicate movements contain fewer

fibers per motor unit



Muscles performing powerful, coarsely controlled movement have larger number of
fibers per motor unit






14

Electrical and Mechanical Events in Muscle Contraction



A twitch is a single contraction
-
relaxation cycle



Muscle Twitch



A mu
scle twitch is the response of the muscle fibers of a
motor unit

to a single action potential
of its motor neuron. The fibers contract quickly and then relax. Three Phases:



Latent Period



time elapsed from the application of a stimulus to the beginning o
f the
contract
ion (when Ca is being released); it’s
the first few ms after stimulation when excitation
-
contraction is occurring



Period of Contraction



cross bridges are active and the muscle shortens if the tension is great
enough to overcome the load



Per
iod of Relaxation



Ca2+ is pumped back into SR
, degradation of ACh

and muscle tension
decreases to baseline level



15


Graded muscle responses




Graded muscle responses are:



Variations in the degree or strength of muscle contraction in response to demand



Req
uired for proper control of skeletal movement



Muscle contraction can be graded (varied) in two ways:



Changing the
frequency

of the stimulus



Changing the
strength

of the stimulus


Motor unit recruitment

-

The process of increasing the number of active mot
or units in a muscle
for stronger contractions


Muscle Response to Stimulation Frequency



A single stimulus results in a single contractile response


a muscle twitch (contracts and
relaxes)



More frequent stimuli increases contractile force


wave summation

-

muscle is already
partially contracted when next stimulus arrives and contractions are summed





More rapidly delivered stimuli result in incomplete tetanus


sustained but quivering
contraction



If stimuli are given quickly enough, complete tetanus res
ults


smooth, sustained contraction
with no relaxation period












16



Summation &

Tetanus



A sustained contraction that lacks even partial relaxation is known
as tetanus



Factors Affecting Force of Muscle Contraction



Number of motor units recruited,

recruitment also helps provide smooth muscle action rather
than jerky movements



The relative size of the muscle fibers


the bulkier the muscle fiber (greater cross
-
sectional
area), the greater its strength



Asynchronous recruitment of motor units

Used t
o prevent fatigue; w
hile some motor units

are active others are inactive
-

this pattern of firing provides a brief rest for the inactive units
preventing fatigue

while maintaining contraction by allowing a brief rest for the inactive units.



Degree of muscle

stretch







17




Length
-
Tension Relationship



Muscle tone




The constant, slightly contracted state of all muscles



Does not produce active movements



Keeps the muscles firm and ready to respond to stimulus



Helps stabilize joints and maintain posture



Due

to spinal reflex activation of motor units in response to stretch receptors in muscles and
tendons


Contraction of Skeletal Muscle Fibers



The force exerted on an object by a contracting muscle is called
muscle tension
, the opposing
force or weight of the
object to be moved is called the
load
.



Two types of Muscle Contraction:

1.

When muscle tension develops, but the load is not moved (muscle does not shorten) the
contraction is called
Isometric

2.

If muscle tension overcomes (moves) the load and the muscle shorte
ns, the contraction
is called
Isotonic


Isometric

Contractions



T
he muscle does not or cannot shorten, but the tension on the muscle increases
, no change in
length



In isometric contractions, increasing muscle tension (force) is measured



18



Isotonic Contrac
tions



In isotonic contractions, the muscle changes length and moves the load. Once sufficient
tension has developed to move the load, the tension remains relatively constant through the
rest of the contractile period.

In isotonic contractions, the amount
of shortening (distance in
mm) is measured
.



Two types of isotonic contractions:



Concentric

contractions


the muscle shortens and does work



Eccentric

contractions


the muscle contracts as it lengthens


Concentric Isotonic Contraction



Energy Sources for

Contraction



ATP is the only energy source that is used directly for contractile activity



As soon as available ATP is hydrolyzed (4
-
6 seconds), it is regenerated by three pathways:



Transfer of high
-
energy phosphate from creatine phosphate to ADP, first ene
rgy
storehouse tapped at onset of contractile activity



Oxidative phosphorylation (citric acid cycle and electron transport system
)

-

takes place
within muscle mitochondria if sufficient O2 is present



Glycolysis
-

supports anaerobic or high
-
intensity exerci
se


CP
-
ADP Reaction



Transfer of energy as a phosphate group is moved from CP to ADP


the reaction is catalyzed
by the enzyme
creatine kinase



Creatine phosphate + ADP


creatine + ATP



Stored ATP and CP provide energy for maximum muscle power for 10
-
15 seco
nds


19




Anaerobic Glycolysis



Glucose is broken down into pyruvic acide to yield 2 ATP



When oxygen demand cannot be met, pyruvic acid is converted into lactic acid



Lactic acid diffuses into the bloodstream


can be used as energy source by the liver, kidn
eys,
and heart



Can be converted back into pyruvic acid, glucose, or glycogen by the liver


Glycolysis and Aerobic Respiration



Aerobic respiration occurs in mitochondria
-

requires O2



A series of reactions breaks down glucose for high yield of ATP



Glucose
+ O2


CO2 + H2O + AT
P


20



Muscle Fatigue



Muscle fatigue


the muscle is physiologically not able to contract



Occurs when oxygen is limited and ATP production fails to keep pace with ATP use



Lactic acid accumulation and ionic imbalances may also contribute

to muscle fatigue



Depletion of energy stores


glycogen



When no ATP is available, contractures (continuous contraction) may result because cross
bridges are unable to detach



Ionic imbalance
, neural fatigue



Central Fatigue


psychological, it hurts


For a

muscle to return to its pre
-
exercise state:

-

Oxygen reserves must be replenished

-

(Lactic acid must be converted to pyruvic acid?)

-

Glycogen stores must be replaced

-

ATP and CP reserves must be resynthesized


Oxygen debt



the extra amount of O2 needed for th
e above restorative processes


Muscle Fiber Type
s
: Speed of Contraction



Speed of contraction


determined by how fast their myosin ATPases split ATP



Oxidative

fibers


use aerobic pathways



Glycolytic

fibers


use anaerobic glycolysis



Based on these two cri
teria skeletal muscles may be classified as:



Slow oxidative fibers (Type I)
-

contract slowly, have slow acting myosin ATPases, and
are fatigue resistant
; postural muscle groups



Fast oxidative fibers (Type IIA)
-

contract quickly, have fast myosin ATPases,
and have
moderate resistance to fatigue
;
Abun
dant is muscle groups requiring

speed (sprinter)



Fast glycolytic fibers (Type IIB)
-

contract quickly, have fast myosin ATPases, and are
easily fatigued
;
large diameter fibers used in muscles requiring strong an
d rapid, but
brief contractions (arms)


21


Smooth Muscle



Occurs within most organs



Walls of hollow visceral organs, such as the stomach



Urinary bladder



Respiratory passages



Arteries and veins



Helps substances move through internal body channels via peristal
sis



No striations



Filaments do not form myofibrils



Not arranged in sarcomere pattern found in skeletal muscle



Is Involuntary



Single Nucleus



Smooth Muscle contraction


22



Composed of spindle
-
shaped fibers with a diameter of 2
-
10

m and lengths of several hun
dred

m



Cells usually arranged in sheets within muscle



Organized into two layers (longitudinal and circular) of closely apposed fibers



Have essentially the same contractile mechanisms as skeletal muscle







Smooth Muscle



Cell has three types of filament
s



Thick myosin filaments



Longer than those in skeletal muscle



Thin actin filaments



Contain tropomyosin but lack troponin



Filaments of intermediate size



Do not directly participate in contraction



Form part of cytoskeletal framework that supports cell shape



Have dense bodies containing same protein found in Z lines



Contraction of Smooth Muscle


23



Whole sheets of smooth muscle exhibit slow, synchronized contraction



Smooth muscle lacks neuromuscular junctions



Action potentials are transmitted from cell to cell



Some smooth muscle cells:



Act as pacemakers and set the contractile pace for whole sheets of muscle



Are self
-
excitatory and depolarize without external stimuli

Stimuli Influencing Smooth Muscle
Contractile Activity
Stimuli Influencing Smooth Muscle
Contractile Activity





Muscle fiber stimulated



Ca2+ released into the cytoplasm from ECF



Ca2+ binds with calmoduli
n



Ca2+/Calmodulin activates mysoin kinase



Myosin kinase phosphorylates myosin



Myosin can now bind with actin




Smooth Muscle Contraction


24

ECF
Ca
2+
Ca
2+
Ca
2+
Sarcoplasmic
reticulum
CaM
P
i
P
i
Active
MLCK
CaM
ADP +
Active myosin
ATPase
Actin
P
P
Intracellular Ca
2+
concentrations increase
when Ca
2+
enters cell
and is released from
sarcoplasmic
reticulum.
Ca
2+
binds to
calmodulin
(
CaM
).
Ca
2+

calmodulin
activates myosin light
chain
kinase
(MLCK).
MLCK
phosphorylates
light chains in myosin
heads and increases
myosin
ATPase
activity.
Active myosin
crossbridges
slide
along
actin
and create
muscle tension.
ATP
Increased
muscle
tension
Ca
2+
Inactive myosin
Inactive
MLCK
1
2
3
4
5
1
2
3
4
5
ECF
Ca
2+
Ca
2+
Ca
2+
Sarcoplasmic
reticulum
CaM
P
i
P
i
Active
MLCK
CaM
ADP +
Active myosin
ATPase
Actin
P
P
Intracellular Ca
2+
concentrations increase
when Ca
2+
enters cell
and is released from
sarcoplasmic
reticulum.
Ca
2+
binds to
calmodulin
(
CaM
).
Ca
2+

calmodulin
activates myosin light
chain
kinase
(MLCK).
MLCK
phosphorylates
light chains in myosin
heads and increases
myosin
ATPase
activity.
Active myosin
crossbridges
slide
along
actin
and create
muscle tension.
ATP
Increased
muscle
tension
Ca
2+
Inactive myosin
Inactive
MLCK
1
2
3
4
5
1
2
3
4
5


Comparison of Role of Calcium in Bringi
ng About

Contraction in Smooth Muscle and Skeletal Muscle


25



Cardiac Muscle

Tissue



Occurs only in the heart



Is striat
ed like skeletal muscle but
has a branching pattern with intercalated Discs



Usually one nucleus, but may have more



Is not voluntary



Contracts at a fairly steady rate set by the
heart’s pacemaker



Neural controls allow the heart to respond to changes in bodily needs