Skeletal Muscle
I. Skeletal Muscle Anatomy
A. Anatomy of a whole muscle (many cells)-review on your own
1. Fascicles & endomysium- muscle cells ("fibers") are arranged in
bundles called fascicles. Connective tissue between cells called endomysium.
Satellite cells are smaller cells in the endomysium, that help to repair damaged
muscle fibers. Each muscle cell is surrounded by blood capillaries and contacts
the end of one motor neuron.
2. Perimysium- connective tissue between fascicles. Larger blood vessels
& nerves run through.
3. Epimysium- dense connective sheath surrounding perimysium and
fascicles
4. Tendons & aponeuroses- epi-, peri-, and endo- mysia merge into one
another at the ends of a muscle and form ropes (tendons) or sheaths (aponeuroses)
of dense connective tissue. The fibers of this dense connective tissue tie into the
fibers of bone, creating an extremely strong attachment.
B. Microanatomy: anatomy of muscle cells
1. Each cell runs the length of the entire muscle. Skeletal muscle cells are
multinucleated (during development, myoblasts fuse). Nuclei get squished to the
outskirts, as the cells are packed with contractile proteins.
2. Myofibrils- within the cell, contractile protein fibers are arranged in
bundles called myofibrils. Myofibrils run the length of the cell.
3. Ion channels and Specialized membranes/organelles of muscle cells (ttubules, sarcoplasmic reticulum, & motor end plate)
a. T-tubules- are invaginations of the cell membrane (muscle cell
membrane called "sarcolemma"). The invaginations form a series of tubes
that wrap around myofibrils in rings. Extracellular fluid fills the t-tubules
(since they are invaginations of the membrane). Remember that the
extracellular fluid contains lots more Na+ than the intracellular fluid; this
will be important for contraction.
b. Sarcoplasmic Reticulum- is the ER of muscle cells, but is
specialized to store Ca2+, and release it on demand. The SR wraps around
myofibrils, between t-tubules. The areas of SR between t-tubules are
called terminal cisternae. Each t-tubule plus its two neighboring cisternae
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are considered a functional unit, called a triad. This is important because
when t-tubules allow Na+ into the cell from extracellular fluid, that event
causes the neighboring cisternae to release Ca2+. The release of Ca2+
from the cisternae will start a contraction.
c. Motor end plate: area of the sarcoplasm. Here is where the
terminals of motor neurons “talk” to muscle cells and tell them to contract.
The neurons release neurotransmitters (specifically, acetylcholine: Ach)
onto the muscle cell at the motor end plate. The motor end plate contains
an abundance of chemically-gated ion channels: Na+ channels that open
when Ach binds.
d. Ion channels/pumps- as previously stated, the motor end plate
contains an abundance of chemically-regulated Na+ channels. The rest of
the sarcoplasm, including along the t-tubules, contains voltage-regulated
Na+ channels. The sarcoplasmic reticulum contains voltage-regulated
Ca2+ channels, and active transport Ca2+ pumps. These are the only types
of channels we will consider for muscle cells, but keep in mind that there
are also gated K+ channels and Na+ and K+ leak channels.
4. The contractile units: sarcomeres.
a. Myofibrils contain contractile proteins that are arranged into
end-to-end units called sarcomeres. Each sarcomere produces a
contraction. Sarcomeres are attached to each other. When a cell contracts,
all sarcomeres along the myofibril contract in unison, and the entire cell
shortens.
b. Each sarcomere has a specific arrangement of protein filaments:
i. The beginning and end of a sarcomere are deliniated by
the Z-line: a mesh of intermediate filaments called connectins. Zlines CONNECT adjacent sarcomeres.
ii. The center of each sarcomere contains a mesh of thick
filaments (myosin) called the M-line.
iii. Thin filaments (actin plus some other proteins) attach to
the Z-line and run toward the central M-line, but don't reach the Mline.
iv. Thick filaments (lots of myosins wrapped around each
other) attach to the central M-line and run toward the Z-line, but
don't reach the Z-line.
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*The area where thin and thick filaments overlap, between the Zline and the M-line, is called the Zone of Overlap. This zone must be
maintained in order for the sarcomere to be able to contract, because in a
contraction, the thick and thin filaments interact.
v. Titin filaments run from the M-line all the way to the Zline. They are connected to both. From the M-line, titin runs right
down the center of the thick filaments. When the thick filaments
end, titin continues on its own to the Z-line. Titin filaments move
with the sarcomeres during contraction, and prevent the
sarcomeres from stretching (lengthening) too much after
contraction. They help to maintain the Zone of Overlap.
vi. Banding patterns: because all of these proteins are
located in specific areas of the sarcomere, and because some areas
are denser with proteins than others, sarcomeres/myofibrils have
patterns of light and dark areas. You need an extremely powerful
microscope to detect these banding patterns; they are not the
striations we see with our microscopes.
a) Z-line: mesh of connectin, where titin and actin
attach. The Z-lines of adjacent myofibrils attach to each
other, and the Z-lines of peripheral myofibrils attach to the
sarcolemma. This is what causes the visible striations we
can see with our standard microscopes.
b) I-band: area of thin fibers and titin only, no
overlap of thin & thick. Includes the Z-line.
c) A-band: start to finish of thick filaments,
including the M line and the zone of overlap.
d) Zone of overlap: where thick & thin fibers
overlap
e) H-band: area of thick filaments only, includes the
M-line but not the zone of overlap.
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II. Muscle Contraction
A. The actual contraction (shortening) of a sarcomere: the relationship & design
of thick and thin filaments
1. Muscle at rest
Thick and thin filaments run parallel to one another. Thick
filaments are composed of many strands of myosin. Each myosin contains
a spring loaded bulbous "head" that sticks out from the thick filament.
Thin filaments are composed of actin, tropomyosin, and troponin.
Actin subunits have "active sites," areas that the myosin heads can bind to.
At rest, tropomyosin covers those active sites, and myosin remains springloaded and unbound to actin.
2. When a contraction is initiated,
Troponin moves tropomyosin out of the way. Myosin heads spring
up and ratchet actin toward the M-line. The sarcomere contracts/shortens.
All sarcomeres are affected and contract together.
B. The whole process
1. Overview- Motor neurons release Ach onto a muscle cell. This causes
Na+ chanels to open and Na+ rushes into the cell. Influx of Na+ causes SR to
release Ca2+. Ca2+ binds to troponin, which causes troponin to move
tropomyosin away from the active sites on actin. Myosin heads spring up, bind to
the active sites, and ratchet actin. Meanwhile, Ach is destroyed by
acetylcholinesterase, and Na+ is actively pumped back out of the cell. ATP is
used to "recock" the myosin heads, or return them to their spring loaded positions.
SR actively pulls Ca2+ back in, Ca2+ is removed from troponin, which causes
tropomyosin to cover active sites again.
-In more detail2. Neural stimulationKey words: neuromuscular junction, motor end plate, resting
potential, action potential. Remember that "membrane potential" refers to
the separation of charged particles on either side of a membrane. Potential
is measured in volts, and cells maintain potentials in milliVolts (mV).
Remember also that membrane potential is a form of stored energy,
because those charged particles would MOVE across the membrane if
they could.
Ach causes Na+ channels at the motor end plate to open, and Na+
rushes in. The influx of positive charges (Na+) changes the voltage of the
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membrane, or the membrane potential. This change in voltage causes more
Na+ channels to open (voltage-regulated channels). This has a domino
effect; as Na+ rushes into one area of the cell (starts at the motor end
plate), adjacent areas open channels and so forth, until the entire
membrane, INCLUDING THAT LINING T-TUBULES, is affected.
*Side note: when you see the term "membrane permeability" for
substances that can't cross by simple diffusion (that need protein
channels), what that term refers to is how many channels are available to
move the substance. For instance, we say a muscle cell changes its
permeability to sodium in response to Ach. All that means is that more
Na+ channels become available.
3. Calcium Release
When the Na+ channels in the t-tubules of triads open (that is,
when the action potential reaches a triad), voltage-regulated Ca2+
channels open in the terminal cisternae of the triad. Ca2+ rushes out and
binds to troponin.
4. Contraction
Ca2+ binds to troponin, which causes it to move tropomyosin from
the active sites of actin. Myosin heads spring up and ratchet actin.
ATP attaches to myosin head, detaching it from actin. ATP splits
into ADP + Pi. The energy released causes the myosin head to recock into
its spring-loaded ("high-energy") conformation. If another active site
becomes available, it will go through the process again. The released ADP
+ Pi can be reconnected into ATP in one of three ways (section IV,
"muscle energetics")
5. Acetylcholine breakdown
In the meantime, Acetylcholinesterase has broken down Ach,
almost immediately after its release. The Na+-K+ exchange pump has
been busily pumping Na+ back out to restore ion concentrations. And, the
SR actively pumps Ca2+ back in. Once all Ca2+ has been returned to the
SR, the contraction ends.
6. Sarcomeres return to their resting lengths by gravity, opposing muscle
action, and recoil of connective tissue. Titin prevents overstretching of
sarcomeres, maintaining the Zone of overlap.
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III. Muscle mechanicsA. Contraction cycles
1.Twitch- latent phase, contraction, relaxation
-the next three "types" of contraction refer to WHEN subsequent neural stimuli are
applied. Additional tension seen in subsequent contractions is caused by the fact that not
all Ca2+ has been returned to the SR, and that enzyme activity and metabolism have
started to step up.2. Wave summation & Incomplete tetanus
3. Treppe
4. Complete tetanus
B. Contraction in whole muscles1. cells take turns contracting and relaxing, so that each cell can recover its
ATP and fuel for making ATP between contraction cycles.
2. Motor units- each motor neuron controls several muscle cells scattered
throughout a whole muscle (although each muscle cell is controlled by a single
neuron). All muscle cells controlled by one motor neuron are referred to as a
motor unit. When their common neuron is stimulated, all of them contract. When
cells take turns resting and contracting, what's really happening is that some
motor units are being stimulated while others are not.
-Side note: strength of a whole muscle contraction (total tension) is determined by the
total number of sarcomeres participating. That is determined by the number of myofibrils
per muscle cell, the number of sarcomeres per myofibril, and the number of cells
participating in the contraction. The more motor units called into action (“recruited”),
the stronger the contraction. And the more myofibrils per cell, the stronger each cell can
contract (you can change the amount of contractile fibers, but not the amount of cells, in a
muscle).3. Muscle tone- in a whole muscle, some motor units are always active.
Motor units of a muscle take turns. This causes muscles to always be "tone," or
slightly tense, even when we're slouched on the couch basking in the warm glow
of TV's warm glow. Muscle tone stabilizes joints and helps keep us warm
(remember that heat is "lost" anytime energy is converted from stored to kinetic,
which happens constantly with the transfer of ATP to ADP + Pi in active muscle).
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C. Types of contractions- based on whole muscle length changes
1. Isotonic- muscle length changes
a. Concentric- muscle shortens, tension overcomes resistance.
b. Eccentric- muscle lengthens, tension is overcome by resistance,
which pulls the muscle. Easiest to understand by thinking about opposing
muscle action: When you lower a weight slowly, your biceps contracts to
slow the movement of the forearm. Even though it's contracting, it's
lengthening because the contraction of the triceps, gravity, and the weight
of the...weight, are overcoming the tension produced by the biceps
contraction.
2. Isometric- muscle does not change length, tension cannot overcome
resistance but resistance doesn't come from a direction that pulls on muscle. Push
your hands together in front of your chest; your muscles contract, but don't
change length.
IV. Muscle Energetics: what individual cells use for energy when
A. Background- cells can use fatty acids & glucose for energy; that is, they can
extract the energy from these substances and use that energy to add ADP + Pi, making
ATP. Glucose can be used to make ATP via an anaerobic pathway (one that doesn't
require oxygen): glycolysis. Glycolysis is relatively fast, but only yields two ATP for the
cell to use. It does not require oxygen or available mitochondria. The biproducts of
glycolysis, and fatty acids, can be used to make ATP via aerobic pathways (require
oxygen). Aerobic respiration (making ATP) is relatively slow, but yields ~36 ATP per
glucose. It also requires oxygen and mitochondria.
B. Resting muscle cells- Use primarily aerobic pathways, and specifically mostly
fatty acids, to generate ATP. Also prepare for the energy demands of contraction by:
keeping enough ATP on hand for a couple seconds of contraction, storing glucose in the
form of glycogen, and storing energy in the compound creatine phosphate (CP). CP
stores energy, and the cell can use that energy to combine ADP and Pi extremely quickly,
even more quickly than via glycolysis. A resting muscle fiber makes more ATP than it
needs, and it uses the excess ATP to create all of the storage mentioned above (glycogen,
CP). Cells must store energy in these forms because it simply can't make enough ATP,
and store it directly, to power normal contractions. ATP doesn't store well (it breaks
down relatively quickly).
C. A muscle cell contracts
1. In the first few seconds of contractions, the cell uses its scant ATP
reserves.
2. In the next few seconds (~15 sec), CP molecules split, and the energy
released is used to reattach ADP & PO4, generating more ATP.
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3. In the meantime, glucose molecules are being split (glycolysis) and
aerobic respiration steps up. Glycolysis alone can generate enough ATP for about
2 minutes.
4. In the meantime, aerobic respiration has begun to extract energy from
glycolysis’ leftovers and from fatty acids. Aerobic respiration starts to catch up
with demands in a couple of minutes, and can supply energy for sustained periods
of time.
-Remember that cells take turns resting and contracting. Before ATP runs out, contracting
cells relax, and relaxing cells take over. When energy demands are high, like when you're
working out or running from a lion, more cells are called into action, and blood gets
shunted to muscles which brings in more O2 and supports aerobic respiration. If you
conduct a strong contraction "cold" (like suddenly lifting a heavy weight or scrambling
up a tree to escape a lion that suddenly appears), you split tons of glucose suddenly. If
you work up from lighter contractions to stronger contractions (like warming up or
walking to find animal tracks before running to catch up to your prey), you split less
glucose, and allow time for aerobic respiration to step up to meet energy demands.D. Types of muscle fibers (cells)- based on their primary energy source and speed
of contraction. Whole muscles are composed of a mixture of these cell types.
1. Fast Glycolytic fibers
Contract quickly, powerfully. Use mainly anaerobic pathways.
Fatigue quickly. Few mitochondria & little myoglobin, lots of glycogen &
myofibrils. Great for sudden, strong contractions; the type you might need
to scramble up a tree to get away from a lion that suddenly appears, or to
throw a boulder at that lion. Body builders love these types of fibers.
Appear light, called white.
2. Slow Oxidative fibers
Contract relatively slowly. Rely more on aerobic pathways. Lots of
mitochondria & myoglobin, more capillaries. Less glycogen & myofibrils.
Great for endurance contractions, like spending the day gathering berries
& root vegetables. Marathon runners love these fibers. Appear red.
3. Fast Oxidative fibers (Intermediate fibers)
Contract relatively quickly and powerfully, but don't fatigue as
easily as fast fibers. Decent glycogen stores, but also plenty of
mitochondria, mitochondria, and capillaries. You can change some of your
fast fibers to intermediate fibers by participating in endurance exercise. In
humans, many fibers are intermediate. Appear red.
E. Please read “Effect of Exercise on Muscles,” pp 271-272.
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