Musculoskeletal Physiology of MSK

AY 2019-2020 Dr. Paredes

Module 2 8/22/19

fewer muscle fibers (for instance, as

LEARNING OBJECTIVES
● List contractile proteins
● Describe the molecular mechanism of
muscle contraction
● Define Isometric, Eccentric, Isotonic
contraction
● Describe length tension relationship
● Describe the relation between load and
velocity of contraction
● Understand force summation
● Describe neuromuscular junction
● Understand motor unit
● List the type of muscle fibers
● Describe effects of exercise and
hormones on skeletal muscle
● To be familiar with the electromyography
LEGEND:
few as two or three muscle fibers per
motor unit in some of the laryngeal
muscles).
★ Large muscles that do not require fine
control, such as the soleus muscle,
may have several hundred muscle
fibers in a motor unit.
★ An average figure for all the muscles
of the body is questionable, but a
good guess would be about 80 to 100
muscle fibers to a motor unit.
★ The muscle fibers in each motor unit
are not all bunched together in the
muscle but overlap other motor units
in micro bundles of 3 to 15 fibers.
This interdigitation allows the separate
motor units to contract in support of
one another rather than entirely as
individual segments.

Powerpoint Remember Lecturer Book

● ➢ ❖ ★

MOTOR UNIT

★ Each motor neuron that leaves the

spinal cord innervates multiple muscle
fibers, with the number of fibers
innervated depending on the type of
muscle.
★ ​All the muscle fibers innervated by a
single nerve fiber are called a ​motor
unit​.
★ ​In general, small muscles that react
rapidly and whose control must be
exact have more nerve fibers for

M2L3 Justiniano, Urriza, Valdez ​Transhead: ​Mr. Muscle Dolor 1 of 10

 SKELETAL MUSCLES

● Movement
● Stability
● Thermogenesis
❖ Shivering
● Respiration
● Constriction of Organ
❖ “​Pag pigil ng ihi”

Properties:

● Excitability
● Conductivity
★ Functional unit of the muscle
● Contractility
★ Basic contractile unit
● Extensibility
★ Area between two Z lines
❖ Stretch
○ Z line to Z line= 1 sarcomere
● Elasticity
★ Exhibited by skeletal and cardiac muscles
❖ Ability to return back when
onlyHas thick filaments and thin filaments
stretched
★ Full A band- in the middle

Contractile Proteins
ORGANIZATION OF SKELETAL MUSCLE

From smallest to largest: ➢ Actin

○ AcTHIN
Sarcomeres → Myofibril → Muscle Fiber → ○ Has myosin-binding sites
Muscle Fascicle → Skeletal Muscle ○ At rest: the myosin-binding sites are
covered with ​tropomyosin
Muscle Fiber ➢ Tropomyosin
★ The smallest contractile unit of skeletal ○ Filamentous protein that runs along
muscle the groove of the twisted actin
★ Multinucleated, elongated cell filament.
★ Each contains bundles of filaments called ○ At rest: it ​blocks ​the
myofibril ​that runs along the axis of the cell myosin-binding sites on actin
★ Sarcolemma - cell membrane of the muscle ○ If contraction is to occur: it must
fiber move out of the way to allow
interaction between actin and
Myofibril myosin.
★ It is where the gross striation patterns can be ➢ Troponin
seen ○ Complex of 3 globular proteins (T, I,
★ Each myofibril is essentially in an end-to-end C) located at regular intervals along
arrangement of regularly repeating units the tropomyosin filaments
called the ​sarcomere. ■ Troponin T
● Attaches the
Sarcomere troponin complex
to tropomyosin
■ Troponin I

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 ● Along with
tropomyosin,
facilitates the
inhibition of
myosin binding to
actin
■ Troponin C
● Calcium binding
protein that plays
a central role in
the initiation of
contraction
➢ Myosin
○ Thick filament
○ Contains the myosin head which
binds to actin
NEUROMUSCULAR JUNCTION
★ Skeletal muscle fibers are innervated
by large, myelinated nerve fibers that
originate from large motoneurons in
the anterior horns of the spinal cord.
★ Each nerve fiber, after entering the
muscle belly, normally branches and
stimulates from three to several
hundred skeletal muscle fibers. Each
nerve ending makes a junction, called
the ​neuromuscular junction​, with the
muscle fiber near its midpoint.
★ The action potential initiated in the
muscle fiber by the nerve signal
travels in both directions toward the
muscle fiber ends. With the exception
of about 2 percent of the muscle
fibers, there is only one such junction
per muscle fiber.
★ The nerve fiber forms a complex of
branching nerve terminals that
invaginate into the surface of the
muscle fiber but lie outside the muscle
fiber plasma membrane. The entire
structure is called the ​motor end
plate​. It is covered by one or more
Schwann cells that insulate it from the
surrounding fluids.
★ The invaginated membrane is called
the ​synaptic gutter or synaptic
trough,​and the space between the
terminal and the fiber membrane is
called the ​synaptic space or synaptic
cleft. This space is 20 to 30
nanometers wide.
★ At the bottom of the gutter are
numerous smaller folds of the muscle
membrane called ​subneural clefts​,
which greatly increase the surface
area at which the synaptic transmitter
can act. In the axon terminal are
many mitochondria that supply
adenosine triphosphate (ATP), the
energy source that is used for
synthesis of an excitatory transmitter,
acetylcholine.
★ The acetylcholine in turn excites the
muscle fiber membrane. Acetylcholine
is synthesized in the cytoplasm of the
terminal, but it is absorbed rapidly into
many small synaptic vesicles, about
300,000 of which are normally in the
terminals of a single end plate.
★ In the synaptic space are large
quantities of the enzyme
acetylcholinesterase, which destroys
acetylcholine a few milliseconds after it
has been released from the synaptic
vesicles.
★ How big is gap junction?
➔ 3nm
❖ Synaptic Junction?
➔ 30nm
❖ Neuromuscular Junction?
➔ 50nm
➔ “Malayo kaya gumagamit ng
neurotransmitters”
GENERAL MECHANISM OF MUSCLE
CONTRACTION
The initiation and execution of muscle contraction
occur in the following sequential steps.
★ 1. ​An action potential travels along a motor
nerve to its endings on muscle fibers.
★ 2. ​At each ending, the nerve secretes a
small amount of the neurotransmitter
substance ​acetylcholine.
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 ★ 3. ​The acetylcholine acts on a local area of
In case the qr code doesn’t work:
the muscle fiber membrane to open multiple
“acetylcholine-gated” cation channels
through protein molecules floating in the
membrane.
★ 4. ​Opening of the acetylcholine-gated
channels allows large quantities of sodium
ions to diffuse to the interior of the muscle
fiber membrane. This causes a local
depolarization that in turn leads to opening of
voltage-gated sodium channels. This initiates
an action potential at the membrane.
★ 5. ​The action potential travels along the
muscle fiber membrane in the same way that
action potentials travel along nerve fiber
membranes.
★ 6. ​The action potential depolarizes the
muscle mem- brane, and much of the action
potential electricity flows through the center
of the muscle fiber. Here it causes the https://www.youtube.com/watch?v=ousflrOzQHc
sarcoplasmic reticulum to release large
quantities of calcium ions that have been
stored within this reticulum.
★ 7. ​The calcium ions initiate attractive forces What causes the actin filaments to slide inward
between the actin and myosin filaments, among the myosin filaments?
causing them to slide alongside each other,
which is the contractile process. ★ It is caused by forces generated by
★ 8. ​After a fraction of a second, the calcium interaction of the cross-bridges from the
ions are pumped back into the sarcoplasmic myosin filaments with the actin filaments.
reticulum by a Ca++ membrane pump and ★ In the relaxed state, the ends of the actin
remain stored in the reticu- lum until a new filaments extending from two successive Z
muscle action potential comes along; this discs barely begin to overlap one another
removal of calcium ions from the myofibrils ★ Conversely, in the contracted state, these
causes the muscle contraction to cease. actin filaments have been pulled inward
among the myosin filaments, so their ends
overlap one another to their maximum
MOLECULAR MECHANISM OF MUSCLE
extent.
CONTRACTION

TONE OF MUSCLE

● Tightness of muscle
● Continuous and passive partial contraction of
the ​muscles​, or the ​muscle's resistance to
passive stretch during resting state.
● It helps to maintain posture
● Some fibers are always contracted

Types of Contraction
Scan to watch Sliding Filament Mechanism of Muscle
Contraction ★ Isotonic contraction

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 ○ the force (or tone) is held constant,
and the change in length of the
muscle is then measured.
Has 2 types:
❖ Concentric - causes muscles to
shorten thereby generating force
❖ Eccentric - causes muscles to
elongate in response to greater
opposing force.
➔ More important in sports
★ Isometric contraction
○ muscle length is held constant, and
the force generated during the
contraction is then measured.
❖ Isokinetic - movement at constant speed
regardless of force
Classification of Nerve Fibers
LENGTH-TENSION RELATIONSHIP
★ When muscles contract, they generate force
(often measured as tension or stress) and
decrease in length.
★ When a muscle at rest is stretched, it resists
stretch by a force that increases slowly at
first and then more rapidly as the extent of
stretch increases. This purely passive
property is due to the elastic tissue in the
muscle. If the muscle is stimulated to
contract at these various lengths, a different
relationship is obtained.
★ Specifically, contractile force increases as
muscle length is increased up to a point
(designated L​0 ​to indicate optimal length). As
the muscle is stretched beyond L​0​,
contractile force decreases.
★ A
​ t a very long sarcomere length (3.7 μm),
actin filaments no longer overlap with myosin
filaments, so there is no contraction. As
muscle length is decreased toward L​0​, the
amount of overlap increases, and contractile
force progressively increases.
★ As sarcomere length decreases below 2 μm,
the thin filaments collide in the middle of the
sarcomere, and the actin-myosin interaction
is disturbed and hence contractile force
decreases.
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RELATION OF VELOCITY OF CONTRACTION TO
LOAD
★ A skeletal muscle contracts rapidly when it
contracts against no load to a state of full
contraction in about 0.1 second for the
average muscle.
★ When loads are applied, the velocity of
contraction becomes progressively less as
the load increases
Relation of load to velocity of contraction in a skeletal muscle with a
cross section of 1 square centimeter and a length of 8 centimeters.
★ When the load has been increased to equal
the maximum force that the muscle can
exert, the velocity of contraction becomes
zero and no contraction results, despite
activation of the muscle fiber.
★ This decreasing velocity of contraction with
load is caused by the fact that a load on a
contracting muscle is a reverse force that
opposes the contractile force caused by
muscle contraction.
★ the net force that is avail- able to cause
velocity of shortening is correspondingly
reduced.
FORCE SUMMATION
Adding together individual twitch contractions to
increase the intensity of overall muscle contraction
★ Two ways of Summation in Muscle Fibers
○ Multiple Fiber Summation
○ Frequency Summation
Multiple Fiber Summation
● Increase number of motor units contracting
simultaneously
Size Principle
★ Weak CNS signal (to contract a muscle) =
smaller motor units stimulated, in preference
to the larger motor units
★ As signal strengthens, larger motor units get
excited as well
★ Larger motor units have 50x more contractile
force compared to smaller units
★ Allows gradations of muscle force during
weak contraction in small steps, then
progress to greater contraction, or force,
from larger motor units if needed so
★ This happens because small motoneurons in
the spinal cord are more excitable than the
larger ones, hence they naturally are excited
first
★ Different motor units are driven
asynchronously by the spinal cord, making
contraction alternating among motor units,
thus providing smooth contraction even at
low frequencies of nerve signals
Frequency Summation and Tetanization
★ Left side:
○ Individual twitch contractions
happening one after another at low
frequency of stimulations
★ Right side:
○ As frequency increases, a new
contraction occurs before the
preceding one is over
○ The total strength of contraction
rises progressively with increasing
frequency as both contractions act
together
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 ○ When frequency reaches a critical
level, contractions become so rapid,
they fuse
○ When they fuse, the whole muscle
contraction appears to be smooth
and continuous. (​Tetanization​)
○ At a slightly higher frequency rate,
contraction strength reaches its
maximum so any additional
increase in frequency after that has
no further effect in increasing
contractile force
○ This happens because enough
calcium ions are maintained in
muscle sarcoplasm, so the full
contractile state is sustained
without allowing any relaxation
between action potentials
TYPES OF MUSCLE FIBERS
★ Every muscle of the body is composed
of a mixture of so-called fast and slow
muscle fibers, with still other fibers
gradated between these two extremes.
★ Muscles that react rapidly, including
the anterior tibialis, are composed
mainly of “fast” fibers with only small
numbers of the slow variety.
★ Muscles such as ​soleus that respond
slowly but with prolonged contraction
are composed mainly of ​“slow”​ fibers.
★ The differences between these two
types of fibers are described in the
following sections.
Slow Fibers (Type 1, Red Muscle). The
following are characteristics of slow fibers:
★ Slow fibers are smaller than fast
fibers.
★ Slow fibers are also innervated by
smaller nerve fibers.
★ Compared with fast fibers, slow fibers
have a more extensive blood vessel
system and more capillaries to supply
extra amounts of oxygen.
★ Slow fibers have greatly increased
numbers of mitochondria to support
high levels of oxidative metabolism.
★ Slow fibers contain large amounts of
myoglobin, an iron-containing protein
similar to hemoglobin in red blood
cells. Myoglobin combines with
oxygen and stores it until needed,
which also greatly speeds oxygen
transport to the mitochondria. The
myoglobin gives the slow muscle a
reddish appearance and hence the
name red muscle.
Fast Fibers ​(Type II, White Muscle)​. The
following are characteristics of fast fibers:
★ Fast fibers are large for great strength
of contraction.
★ An extensive sarcoplasmic reticulum
is present for rapid release of calcium
ions to initiate contraction.
★ Large amounts of glycolytic enzymes
are present for rapid release of
energy by the glycolytic process.
★ Fast fibers have a less extensive
blood supply than do slow fibers
because oxidative metabolism is of
secondary importance.
★ Fast fibers have fewer mitochondria
than slow fibers, also because
oxidative metabolism is secondary. A
deficit of red myoglobin in fast muscle
gives it the name white muscle.
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 EFFECTS OF EXERCISE & HORMONES ON
SKELETAL MUSCLES ELECTROMYOGRAPHY

★ Muscles that function under no load, no
matter the number of hours in training,
increase little in strength
★ Muscles that contract more than 50% max
force of contraction will develop strength
rapidly even if the contractions are
performed only a few times each day
★ Six nearly maximal muscle contractions
performed in three sets 3 days a week give
approximately optimal increase in muscle
strength, without producing chronic muscle
fatigue
★ Diagnostic procedure to assess the health of
muscles and innervations
★ Can reveal nerve and muscle dysfunction,
and nerve-to-muscle transmission
★ EMG uses tiny devices called electrodes to
translate signals into graphs, sounds, or
numerical values that are then interpreted
★ Needle EMG
○ Needle inserted to muscle to record
electrical activity
★ nerve conduction study
○ Uses electrode stickers/surface
electrodes to measure speed and
strength of signals travelling
between two or more points

REFERENCES

● Guyton p.91
● Berne and Levy Physiology

Muscle Hypertrophy

★ Affected by heredity and level of

testosterone secretion
★ Exercise increases hypertrophy to about
30-60%
★ Increase in diameter of muscle fibres
★ Increase numbers of myofibrils
★ 120% increase in mitochondrial enzymes
★ 60-80% increase in the components of the
phosphagen metabolic system, both ATP
and phosphocreatine
★ 50% increase in stored Glycogen
★ 75-100% increase in stored triglyceride (fat)
★ Increase maximum oxidation rate and
efficiency of the oxidative metabolic system
as much as 45%

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APPENDIX

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