Muscle

1. Describe the structure of skeletal muscle tissue and its connective tissue components

• Skeletal muscles
o Contractile cells
o Connective tissue

• Contractile elements
o Thin and thick filaments – bundled into myofibrils
 The myofibrils that are packed into a muscle cell are composed of
individual contractile elements called myofilaments.
 There are two types of myofilaments:
o The thin filament is composed mainly of the protein actin.
o The thick filament is made up chiefly of the protein myosin

 Myofilament arrangement
 A band
o thick filaments.
o Length of a myosin filament
 I band
o thin filaments only
o contains actin filament only
 Z-disc
o anchors thin filaments, connects adjacent myofibrils
o area between 2 z-discs = sarcomere(functional unit of
skeletal muscle)
 H zone
o only thick filaments
o contains myosin filament only
 M line
o H zone center; connects thick filaments
o Where myosin filaments are anchored
 Sarcomere
o contractile unit

• A useful acronym is MHAZI 

o the M line is inside the H zone which is inside the A band, whilst the Z line is
inside the I band.
• Sarcolemma
o Cell surface membrane of a single cell which forms one muscle fibre
• Transverse Tubules (T-tubules)
o Unique to muscle cells
o Invaginations of the sarcolemma that conduct charge when the cell is depolarized
o Surround myofibrils
o Connects with other T-tubules
o Function: conducts Aps from surface to interior
• Sarcoplasmic reticulum
o Specialised endoplasmic reticulum
o Contains a large store of calcium ions in terminal cisternae
o Surround myofibrils
o Connected across fiber width but not length
o Initiates contraction by releasing calcium when prompted by T-tubules
• Epimysium
– Covers the whole muscle
• Fascia
– Connective tissue outside the epimysium
– Surrounds and separates the muscles

• Perimysium
– surrounds fascicles (muscle cell bundles)
– Conduit for nerves and blood vessels
– Divides the muscle fibers into bundles or fascicles

• Endomysium
– Innermost connective tissue
 – Covers each muscle fiber or cell
– separates, electrically insulates muscle cells.

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2. Describe the ultrastructure of the skeletal fiber

 Skeletal muscle consists of number of muscle fibers lying parallel to one another and bundled
together by connective tissues
 Fibres usually extend the length of the muscle
 During embryonic development, huge skeletal muscle fibers are formed by the fusion of
many smaller cells (>100) called myoblasts

Structure of skeletal fiber

• Numerous myofibrils
o Specialized intracellular structure of muscle cells that contain contractile
apparatus
 Constitutes 90% of volume of muscle fibre
o Each myofibril consists of a regular arrangement of
 Thick filaments
 Thin filaments

Whole → muscle → myofibril → thick and thin → myosin and

muscle fibre filaments actin
(an organ) (cell) (a specialized intracellular (cytoskeletal (protein
structure) elements) molecules)
3. Composition of the thick and thin filaments

Thick filaments
• Special assemblies of the protein myosin
o Myosin
• Myosin lies lengthwise with their tail toward centre of the filament and head towards
outwards
o these heads form cross bridges between the thick and thin filaments
• composed of approximately 400 myosin molecules, 200 arrayed on either side of the M
line

Thin filaments
• Made up of three proteins

o Actin
 Primary structural protein of the thin filament
 Each actin molecule has a special binding site for attachment with a
myosin cross bridge
 Binding of myosin and actin molecules at the cross bridge results
in energy-consuming contraction of the muscle fibre
o Tropomyosin
o Troponin

 in a relaxed muscle fibre, contraction does not take place…

- actin cannot bind with cross bridges because of the way tropomyosin and
troponin are positioned within the thin filament
- tropomyosin covers the actin sites that bind with the cross bridge,
blocking the interaction that leads to muscle contraction
- troponin is made up of three polypeptide units
- one binds to tropomyosin
- one binds to actin
- one can bind to calcium

Organization of thick and thin filaments

• Hexagonal lattice
 • 6 thin filaments ‘thick filaments
• The basic arrangement of the myofilaments within each myofibril is repeated over and
over again all along its length. The repeating unit of organized myofilaments is called a
sarcomere. The sarcomere is the basic structural unit of skeletal muscle.
• Within a sarcomere the thick and thin filaments interdigitate so that in cross section they
are seen to form a hexagonal lattice, in which 6 thin filaments are arrayed around each
thick filament. The thick filaments are also arranged hexagonally to each other.
• Note that the pattern of thick and thin filaments seen in cross section will change
depending on where within the sarcomere the section is taken

A thick filament is. These molecules are maintained in bundles by the C protein (clamp
protein), M line protein and the hydrophobic interactions of the myosin molecules
themselves. A single myosin molecule is like two golf clubs with the handles twisted
together and is formed by one heavy chain and its two associated light chains.

4. explain the sliding filament mechanism of muscle contraction

• contraction of a muscle cell occurs as the thin filaments slide past the thick filaments.
During contraction, the sarcomere shortens, the thin and thick filaments overlap to a
greater degree, and the muscle shortens
o neither thin nor thick filaments decrease in length to shorten sarcomere
 instead, contraction is accomplished by the thin filaments sliding closer
together between the thick filament

• I band decreases, A band remains constant

• Filaments do not change length, only position: Z lines come together

i. during contraction, thin filaments on each side of sarcomere slide inward over the
stationary thick filaments toward the A band’s centre
ii. as they slide inward, thin filaments pull the Z lines closer together so the sarcomere
shortens
iii. as all of sarcomere thoughtout the muscle fibre is shortened, entire fibre shortens
iv. when a muscle fibre contracts, moving the Z lines closer together, muscle fibre and whole
muscle shortens

Called concentric contraction

• The H zone, in the centre of the A band where the thin filaments do not reach,
becomes smaller as the thin filaments approach each other when they slide more
deeply inward.
 • The I band, which consists of the portions of the thin filaments that do not overlap
with the thick filaments, narrows as the thin filaments further overlap the thick
filaments during their inward slide.
• The thin filaments themselves do not change length during muscle fibre shortening.
• The width of the A band remains unchanged during contraction, because its width is
determined by the length of the thick filaments, and the thick filaments do not change
length during the shortening process.
• Note that neither the thick nor the thin filaments decrease in length to shorten the
sarcomere.
• Instead, contraction is accomplished by the thin filaments from the opposite sides of
each sarcomere sliding closer together between the thick filaments.

5. Cross bridge and cross-bridge cycling

Cross bridge
• The attachment of myosin with actin within the muscle cell
• After binding, myosin changes its shape, pulling actin towards the middle of the
sarcomere
• ATP binds to myosin, thus detaching the cross bridge
o Provides energy for yet another cycle to occur

cross-bridge cycling
• Repeated attachment of actin and myosin

5. Summarize the main features of excitation-contraction coupling and explain the role of Ca2+

 Excitation is how nervous stimulates an action potential in the muscle sarcolemma

 in order for a skeletal muscle to function, it must contract
Series of events that link these two phases is called excitation contraction coupling

Steps
1. AP spreads from motor endplate in all direction
2. when the wave of excitation reaches the transverse tubule (T-Tubule), it continues
down into sarcoplasm of the muscle fiber
3. AP stimulates the opening of voltage gated ion channels in the T-Tubule. These
channels are physically linked to Calcium channels in sarcoplasmic reticulum
4. Calcium channels open
- Calcium concentration is higher in the sarcoplasmic reticulum than sarcoplasm
- they diffuse out and into the cytosol
5. Calcium ion binds to troponin of thin filaments
 6. This binding causes troponin tropomyosin complex to change shape and move into
the groove on the actin
7. exposes active sites on actin filament
8. active sites are available to myosin heads, which are the main protein of the thick
filament

6. Describe the neuromuscular junction and outline the steps involved in neuromuscular
communication

Neuromuscular junction
• a type of synapse where neuronal signals from the brain or spinal cord interact
with skeletal muscle fibers, causing them to contract.

steps
1. AP arrives at axon terminal of motor neuron.
2. Voltage-gated Ca2+ channels open. Ca2+ enters axon terminal.
3. Ca2+ entry causes acetylcholine (ACh) release by exocytosis.
4. ACh diffuses across synaptic cleft and binds to ACh receptors (AChRs) on the
sarcolemma.
5. ACh binding opens ligand-gated ion channels that passage of Na+ and K+ which produces
a local depolarization called the end plate potential (EPP).
6. ACh effects are terminated by
its breakdown in the synaptic cleft by acetylcholinesterase (AChE) and diffusion away
from the junction.
Parts to know

Axonal ending
: synaptic vesicles contain AcH (Neurotransmitter)

Motor End Plate

: specialized part of the sarcolemma (high folded) that contains nicotinic acetylcholine
receptors (nAcHRs)

Neuromuscular junction is separated by synaptic clef and basal lamina

7. Three Phases of a Muscle Twitch

• A muscle twitch includes three phases: actual times for each phase varies with specific
muscle being studied
1. Latent Phase: sarcolemma and T-tubules depolarize. Ca2+ released into cytosol and
cross-bridges begin to cycle. The number of cross-bridges not sufficient to visibly shorten
muscle. Lasts < 5 msec
2. Contraction Phase: sarcomeres shorten as a result of myosin cross-bridge cycling.
continues until peak tension. Speed with which this phase occurs depends on the load
being lifted and the fiber type: fast- or slow-twitch.
3. Relaxation Phase: Ca2+ in cytosol rapidly decreases - actively transported back into
terminal cisternae. Cross-bridge cycling decreases and stops. Tension (force) is reduced,
allowing the muscle to return to its original length.

8. Types of Muscle Contractions

• In an isotonic (concentric) contraction

o the peak tension exceeds the resistance of the load resulting in shortening of the
muscle and movement of the load. This occurs when you use your muscles to
successfully push or pull an object. In an eccentric contraction, the muscle
lengthens.
• Isometric contraction
Peak tension < load. the muscle contracts and develops tension, but its length does
not change. This occurs when a muscle attempts to push or pull an immovable
object.

9. Overview of ATP Synthesis in Muscle

 • When ATP supplies are low, muscle cells use three processes to synthesize
additional ATP
o Hydrolysis of creatine phosphate
o Glycolysis
o Krebs cycle (citric acid cycle) and oxidative phosphorylation

• Creatine phosphate
o At rest, muscle fibers produce more ATP than they need.
 Excess ATP used to synthesize creatine phosphate or
phosphocreatine (PCr).
o Creatine kinase (CK) transfers high energy phosphate group to creatine.
o Muscle cells use this PCr to store energy. Normal metabolism cannot
produce energy as quickly as a muscle cell can use it, so an extra storage
source is needed.
o During exercise, PCr serves as an immediate reserve of high-energy
phosphates groups, which is used to replenish ATP - for first few seconds
of intense activity.
o Elevation of CK in blood is an indication of muscle damage. Clinically,
CK is assayed in blood tests as a marker of myocardial infarction (heart
attack), rhabdomyolysis (severe muscle breakdown), muscular dystrophy,
and acute renal failure.

10. Types of fibers

• White, fast-twitch Muscle fibers

o Also called glycolytic fibers or Type IIB fibers

o Larger in diameter
o Light in color due to reduced myoglobin
o Surrounded by few capillaries
o Relative few mitochondria
o High glycogen content
o White fast-twitch fibers are large in diameter and are much paler than the red
slow-twitch fibers. The white color is due to the relatively low amounts of
myoglobin, a red-colored oxygen carrying molecule and fewer mitochondria
(which have red pigmented cytochrome complexes).
o They are surrounded by few capillaries and have relatively few mitochondria, thus
white fast-twitch fibers cannot depend on oxygen when making ATP. As a result,
white fibers are anaerobic and get most of their energy from glycolysis.
o Because of their large glycogen reserves, white fibers are often called glycolytic
fibers.
 o As their name suggests, these fibers contract very fast. This speed is due to the
ability of their myosin ATPases to break down ATP very fast, resulting in a very
fast contraction cycle.
o White fast-twitch fibers are found in many of the muscles of the legs and arms of
an animal. For instance in humans, the calf muscle is involved in jumping. Such
an explosive and short contraction requires white-fast-twitch fibers in the muscle.
o As white fibers contract, they generate large quantities of lactic acid, a by-product
of glucose breakdown. This build-up of lactic acid quickly leads to inactivation of
the muscle. Therefore, white fast-twitch fibers tire very easily, and are generally
used for short bursts of activity. But even though white fast-twitch muscles can
only act for a short time, their large diameter allows the muscle to contract very
powerfully.
o Strength training produces increases in the size, strength and glycogen content of
fast glycolytic fibers (they may be 50% larger than in a sedentary person or an
endurance athlete)

• Red slow twitched fibers

o Also called Slow, Oxidative Fibers or Type I Fibers
o small in diameter.
o Their red color comes from the plentiful supply of the oxygen carrier molecule
myoglobin, which has a distinct red color. The myoglobin molecules bind oxygen
and increase the rate of oxygen diffusion throughout the muscle cell.
o Red slow-twitch fiber cells have many mitochondria (which also have red
pigmented cytochrome complexes) and a extensive blood vessel network but few
glycogen reserves.
o These features, along with the strong presence of myoglobin, make the red slow-
twitch fibers highly aerobic. For this reason, they are oxygen dependent and are
often referred to as 'oxidative fibers.‘ They are also called Type I fibers, based on
their myosin ATPase activity.
o Because red fibers can function entirely through aerobic pathways, they are
extremely fatigue resistant. Red fibers have a very high endurance and can
contract for extended periods of time without tiring.
o Despite their high endurance, they do not generate much power because of their
small diameter.
o Their name results from the presence of the slow acting myosin ATPases. Due to
this slow step in the cross-bridge cycle, the contraction of red slow-twitch fibers is
slower than contraction of the other two fiber types, hence the name slow-twitch.
o Red slow-twitch fibers are mainly found in muscles that maintain posture.
Postural muscles have to contract for long periods of time but do not have to be
powerful.

• Intermediate fast twitched fibers

o Type IIa fibers or Fast Oxidative-glycolytic
 o As their name suggests, these fibers have properties of both white fast-twitch and
red slow-twitch muscle fibers.
o They are pinkish in color due to their intermediate levels of myoglobin.
o Fast acting myosin and mostly use oxidative phosphorylation to generate ATP,
but they have some glycogen stores.
o Moderately resistant to fatigue.
o The way this stain is believed to work is as follows. The pre-incubation pH
inactivates the myosin-ATPase enzyme of specific fiber types. The remaining
active enzyme is attached to a calcium atom which is replaced by a cobalt and
finally precipitated as a black insoluble compound by the ammonium sulfide.
o As their name suggests, these fibers have properties of both white fast-twitch and
red slow-twitch muscle fibers.
o They are pinkish in color due to their intermediate levels of myoglobin.
o They have a fast acting myosin and mostly use oxidative phosphorylation to
generate ATP, but they have some glycogen stores. As such, they are moderately
resistant to fatigue.

11. Skeletal, cardiac, smooth muscle

Skeletal : elongated, peripheral nuclei, striations, voluntary.

Cardiac : branching cells, central nucleus, striated, involuntary
Smooth : spindle-shaped , single nucleus, no striation s, involuntary.

Skeletal Cardiac Smooth