In this unit you will learn about the contractile machinery in skeletal muscle fibers (cells), and how that
machinery is activated. Muscle cells are packed with myofibrils. Myofibrils contain an orderly array of muscle
contractile filaments (myofilaments). Myofilaments are aggregates of protein molecules, and are mainly of two
types: thick (myosin) filaments and thin (actin) filaments. The orderly arrangement of thick and thin filaments
gives skeletal muscle its striated appearance (hence the term "striated muscle").
In the presence of ATP and calcium, the myofilaments interact with each other (crossbridge formation)
and pull on the ends of the sarcomeres (see figure 123, page 411 of the text). In this unit, you will learn the
details of this force generation at the sarcomere level (the slidingfilament mechanism), and learn that calcium
concentration at the myofilaments is an important determinant of the degree of force generation. The signal that
initiates the internal release of calcium (and consequently contraction) is the muscle cell action potential
spreading across the cell surface and down invaginations called transverse (T) tubules. These action potentials do
not arise in a spontaneous fashion. Rather, they are the outcome of a nerve action potential reaching the branched
endings of a motor neuron that services the muscle cell in question.
The branched endings come into close proximity of the muscle cell membrane at the end plate within the
neuromuscular junction (NMJ). You will learn about the structure of the NMJ, how ACh is released into the
synaptic gap there, and how this elicits an end plate potential(EPP) in the postsynaptic muscle membrane. The
EPP depolarizes neighbouring muscle membrane, and thereby initiates the action potential that spreads
throughout the muscle cell and triggers contraction.
You will then learn about force (or tension) development in muscle cells and muscle bundles. When
muscle develops tension (contracts) it may shorten, and move an object (load). This is isotonic contraction. On
the other hand, muscle may develop tension against an immovable object (load), for example a wall. This is
isometric contraction. Most of our activity involves a combination of these.
The degree of tension developed by a single muscle fiber is dependent on its precontraction length;
there is an optimal length, above and below which tension development is restricted. A further factor in tension
development is the frequency of nerve stimulation: high stimulus frequencies lead to fusion of individual
contractions, and a maximal contractile effort termed tetanus. A further factor is the number of muscle cells
activated; the larger the number of motor units activated, the larger the tension developed. Muscle contraction is
heavy duty work, and requires a lot of ATP. Skeletal muscle cells have well developed energy metabolism
systems to supply this ATP.
In the body, muscles exert their force on bones via connecting tendons. Broken bones can disrupt this
forcegenerating machinery, as can inflammation of tendons (tendinitis). However, several problems can arise
with the muscle themselves. Fatigue is a common occurrence when muscles are exercised at maximum level for
a short time (as in a sprint), or at a submaximal level for a long time (as in a marathon). The muscle types that
undergo fatigue in the two activities mentioned are distinctly different (white and red, respectively). Aside from
fatigue, heavy muscle work can lead to muscle cramps.
More insidious are some of the diseases that can affect skeletal muscle. These include a fairly frequent
genetic disorder called muscular dystrophy, and an autoimmune disease that results in NMJ degeneration,
Chapter 12 begins with a short discussion of the similarities and differences between skeletal, cardiac,
and smooth muscle. Take this as orientation since you will be covering smooth muscle in Unit 2, and cardiac
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muscle when you come to Module 9.
The first major topic of this unit is the structure and operation of the basic contractile unit of skeletal
muscle, the sarcomere. This is well presented in Figures 123, 128, 129, and 1210.
• The contractile unit of a myofibril
• Has the following elements
o 2 Z disks which are the attachment sites for thin filaments
o I band – Z disks run through the middle of every I band, so each half of an I band belongs to a
o A band – Thick and thin filaments overlap at the outer edges
o H zone is occupied by thick filaments only
o M line form the attachment site for thick filaments; each M line divides an A band in half
• Actin and myosin filaments form a lattice of overlapping thick and thin filaments, held in place by their
attachments to the Zdisk and Mline proteins respectively
The neuromuscular junction is introduced in Chapter 11 on page 398 to 400. It's involvement in excitation
contraction coupling starts on page 417 and is depicted in figure 1211.
• The synapse of a somatic motor neuron and a skeletal muscle fiber
• 3 components
o The motor neuron’s presynaptic axon terminal filled with synaptic vesicles & mitochondria
o The synaptic cleft
o The postsynaptic membrane of the skeletal muscle fiber
• Consists of axon terminals, motor end plates on the muscle membrane ad Schwann cell sheaths
o Somatic motor neuron branches at its distal end
o Motor end plate is a region of muscle membrane that contains high concentrations of ACh
Events of the NMJ:
• Action potentials arriving at the axon terminal open voltagegated Ca channels in the membrane
o Calcium diffuses down cell membrane ▯AChcontaining synaptic vesicles release
• ACh diffuses across synaptic cleft and combines with nicotinic receptor channels on the skeletal muscle
o ACh combines with nicotinic receptors or is metabolized by AChE
The nicotinic cholinergic receptor binds 2 ACh molecule ▯Opens a nonspecific
monovalent cation channel
Motor Unit Group of skeletal muscle fibers and the somatic motor neuron that controls
Motor End Plate The specialized postsynaptic region of a muscle fiber.
NMJ The synapse of a somatic motor neuron and a skeletal muscle fiber.
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End Plate Potential (EPP) Depolarization at the motor end plate due to ACh.
General Term Muscle Equivalent
Muscle cell Muscle fiber
Cell membrane Sarcolemma
Modified Endoplasmic Reticulum Sarcoplasmic reticulum
Muscle Fibers (Skeletal Muscle Cells):
• Know diagram of a muscle cell
Muscle Fiber A muscle cell.
Myofibril Bundles of contractile and elastic proteins responsible for muscle contraction;
contractile structures of a muscle fiber.
Myofilament any of the ultramicroscopic threadlike structures composing the myofibrils of
striated muscle fibers.
Sarcomere The contractile unit of a myofibril.
Thin (Actin) Filament An actincontaining filament of the myofibril.
Thick (Myosin) Filament An aggregation of myosin in muscle.
Muscle Contraction Creates Force:
• Major steps leading up to muscle contraction
1. Events at the NMJ convert ACh signal from a somatic motor neuron into an electrical signal at
the muscle fiber
2. Excitationcontraction (EC) coupling is the process when muscle action potentials initiate
calcium signals that activate a contractionrelaxation cycle.
3. Contractionrelaxation cycle explained by the sliding filament theory of contraction
i. One contractionrelaxation cycle is called a muscle twitch
Sliding Filament Theory of Contraction:
• The current model for muscle contraction
• States that muscle proteins slide past each other to generate force
o Overlapping actin and myosin filaments of fixed length slide past one another in an energy
requiring process, resulting in muscle contraction
• Rotation of myosin cross bridges move actin filaments
The Role of Calcium in Contraction:
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• Calcium signal initiate contraction
o Calcium binds to troponin to initiate muscle contraction after being released from the
• Initiation of contraction
1. Ca levels increase in cytosol
2. Ca binds to troponin (TN)
3. TNCa complex pulls tropomyosin away from actin’s myosinbinding site
i. Allows myosin heads to form crossbridges to carry out power strokes
4. Myosin binds to actin and completes the power stroke
5. Actin filament moves
The Role of Troponin & Tropomyosin in Muscle:
• Troponin is a complex of 3 proteins that is associated with tropomyosin
o Ca must bind to troponin to initiate muscle contraction
o Once bound can move tropomyosin from actin’s myosin binding sites
• Tropomyosin blocks the myosinbinding site on actin
o Tropomyosin must be completely away from actin’s myosinbinding sites in order for myosin
heads to form cross bridges and move the actin filament
• AKA ttubules
• Invaginations of the muscle fiber membrane, associated with the sarcoplasmic reticulum
o Rapidly move action potentials from the cell surface into the interior of the fiber
o Without ttubules, action potentials would be MUCH slower which would delay the response
time of the muscle fiber
• The sequence of action potentials and Ca release that initiate contraction
• Converts an electrical signal into a Ca signal
• 4 major events
o ACh is released from the somatic motor neuron
o ACh initiates an action potential in the muscle fiber
o The muscle action potential triggers Ca release from the sarcoplasmic reticulum
o Ca combines with troponin and initiates contraction
EC Coupling – In Depth StepbyStep Analysis:
1. Somatic motor neuron releases ACh at an NMJ
2. Net entry of Na through ACh receptor channel initiates a muscle action potential
3. Action potential in ttubule alters conformation of DHP receptor
4. DHP receptor opens channels in sarcoplasmic reticulum and Ca enters cytoplasm
5. Ca binds to troponin, allowing actinmyosin binding
6. Myosin heads execute power stroke
7. Actin filaments slides toward center of sarcomere
Learn that the endplate potential results from acetylcholine's action on receptorchannels, and is NOT an
action potential. Be able to sketch a neuromuscular junction.
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