Human Physiology
Lecture 1 – Buwalda – Skeletal muscles
Skeletal muscles are muscles which are attached to bones of the skeleton. These muscles are
voluntary muscles, which can be moved consciously and contract only in response to a signal from a
somatic motor neuron and can not initiate its own contractions. Besides they are striated muscle
tissue, which represents muscle tissue that contains functional units called sarcomeres.
The somatic motor pathway starts at a nerve that targets skeletal muscles
A single motor neuron can control many muscle fibers at one time. The amount depends on
the size of the muscle. The difference between the somatic motor pathway and the
parasympathetic and sympathetic pathway is that there is no ganglion between the nerve
cells of the somatic motor pathway. Besides the somatic motor pathway has only excitatory
effects on muscles, so they will always contract. Whereas in the autonomic pathways signals
can either cause contraction (excitatory) or relaxation (inhibitory) of the muscle cells.
Neurotransmitter: Acetylcholine (ACh)
Receptor: Nicotinic receptor
The somatic motor neuron branches at its distal end, which are called neuromuscular
junctions. These junctions consist of axon terminals, motor end plates on the muscle
membranes and Schwann cell sheaths.
- Schwann cell sheaths are extensions of the
Schwann cells that cover the top of the axon
terminal. These are often myelinated, which
speed up the signal transduction.
- The motor end plate is a region of muscle
membrane that contains high concentrations of
ACh receptors. It is an increased surface of the
muscle membrane, which results in more space
for nicotinic ACh receptors. The synaptic cleft
between the muscle membrane and the axon
terminal is tight and filled with collagen.
The signalling follows the basic principles as other
signalling pathways:
• An action potential arrives at the axon
terminal, causing voltage gated Ca2+
channels to open. Calcium entry
causes synaptic vesicles to fuse with
the presynaptic membrane and
release ACh into the synaptic cleft.
• Na+ depolarized the membrane, which
causes the contraction of muscles
fibers.
• The component α-bungarotoxin is a competitive antagonist for the nicotinic receptors.
The action potential reaches deep into the membrane of the muscle via the T-tubule. A
somatic motor neuron releases ACh at neuromuscular junction. Net entry of Na+ through ACh
, receptor-channel initiates a muscle action
potential. This causes a cascade of reaction which
results in the release of Ca2+ from the
sarcoplasmic reticulum, which eventually results
in the contraction of a muscle.
Because there is no antagonistic reaction on the
somatic motor pathway, the muscle can only
contract via this way. Relaxation of the muscle is
initiated via the motor neuron in the CNS via the
autonomic pathways.
Cells on the muscle can regenerate when there is
loss of muscle fibers. This is done by stem cells
(satellite cells). On a young age this is done
more efficiently than on an older age.
Therefore, older people often suffer from more
muscle loss.
The body contains three types of muscles, which differ
in fiber form and functions:
1. Skeletal muscles fibers are large, multinucleate
cells that appear striped or striated under the
microscope.
- Locomotor movement
- Connected to bone
- Voluntary
2. Cardiac muscles fibers are also striated but they
are smaller branched, and uninucleate. Cells are
joined in series by junctions called intercalated
disks.
3. Smooth muscles fibers are small and lack striations.
- Cardiac muscle and smooth muscle are both responsible for movement of
content
- They are both not connected to bones and are both involuntary
Antagonists skeletal muscle groups move bones in opposite directions. Muscle contraction can pull on
a bone but cannot push a bone away.
Flexion moves bones closer together. For example, when doing an arm curl, the radius and ulna move
towards the humerus.
Extensions moves bones away from each other. For example, when doing a push-up, the radius and
ulna move away from the humerus.
Muscles have another terminology than other
cells, which are more often used when talking
about muscles.
,The anatomy of skeletal muscles
▪ The muscle fascicles are bundles of
muscle fibers.
▪ The t-tubules are responsible for the
whole depolarization of the muscle cell.
▪ The sarcoplasmic reticulum is where
the Ca2+ is stored
▪ Myofibrils are made of sarcomeres,
the functional units of a skeletal muscle.
Sarcomeres consists of multiple
components which can contract or relax
the muscle.
They contain:
- Contractile proteins: actin and
myosin
- Regulatory proteins: tropomyosin
and troponin
- “Giant accessory” proteins: titin and
nebulin
Myosin is a motor protein, which contains “heads”. These heads bind to actin and “walk” over the
actin. In the sarcomere myosin is recognized by the thick filament.
Actin is formed like a helix and G(lobular)-actin molecules. Around actin runs tropomyosin, with
troponin on it. The actin filament is recognized by the thin filament of the sarcomere.
Because of the tropomyosin the myosin can not attach to the actin. This is, however, pushed away by
Ca2+ binding to troponin.
Titin is attached to the myosin is an
elastic protein, which links the end of the
filament to the Z-disc.
Nebulin is linked to the actin filament and
helps to align the filament. It is inelastic.
When the muscle is contracted the thick
and think filament are not shortened.
Therefore, the A-band keeps its length
and the H- and I-band are shortened. The
filaments are sliding into each other.
Muscle contraction
- Initiation of contraction
The Ca2+ levels increase in the cytosol, which causes the binding of Ca2+ to troponin. The troponin-
Ca2+ complex pulls the tropomyosin away from the actin’s myosin-binding site. Myosin can now
bind to the actin and complete a power stroke, which results in the movement of actin filament.
- The contraction
ATP binds to the myosin and the myosin released the action. Myosin then hydrolyses ATP; the
myosin head rotates and binds to actin. The head of myosin binds to G-actin forming a cross
bridge and when Pi is released the hinge moves and moves actin toward the M-line. This is the
basis of muscle contraction, called a power stroke. Myosin then released ADP and the cycle starts
from the beginning.
ATP is needed for muscle contraction and therefore there is a sufficient amount of ATP available in the
relaxation muscle. When there’s a lack of ATP in the muscle a person suffer from rigor mortis.
, The way of excitation of neuronal motor cells to contraction.
ACh is released in the neuromuscular junction and
Na+ gets into the muscle fiber. This causes
depolarization and the transduction of an action
potential. The action potential in the t-tubule alters
a conformation of the DHP receptor. The DHP
receptor opens RyR Ca2+ release channels in the
sarcoplasmic reticulum and the Ca2+ enters the
sarcoplasm. Myosin heads execute power strokes and the actin filaments slides toward the center of
the sarcomere.
Relaxation goes as follows:
Sarcoplasmic Ca2+-ATPase pumps Ca2+ back into the
sarcoplasmic reticulum. This decrease in free
sarcosolic Ca2+ cause Ca2+ to unbind from troponin.
Tropomyosin re-covers binding site. When myosin
heads release elastic elements pull filaments back to
their relaxed position.
One contraction-relaxation cycle is called a twitch → one action potentail in a muscle fiber produces
one twitch.
Energy supply of the skeletal muscles
With the available ATP in the muslces around 8 twitches can
occur. However the muscle gets energy from other sources:
- Phosphocreatine in muscle fiber, activated by kinase
creatine
- Metabolic production of ATP
Glucose via glycolysis to pyruvate → pyruvate to acetyl
CoA → citric acid cycle: 30 ATP
Glucose to lactate via the anaerobic pathway: 2 ATP
FFA’s in the citric acid cycle (β-oxidation)
In the body there are slow- and fast-twitch fibers:
- Slow-twitch oxidative muscle fibers have a smaller diameter, are darker in colour due to
myoglobin and are fatigue resistance.
- Fast-twitch glycolytic muscle fibers have a larger diameter, are paler in colour and are easily
fatigued.
Central fatigue is caused by psychological effects,
whereas peripheral fatigue has also physiological
effects, like depletion, lazy muscle and accumulation
of lactate, which lowers the pH in the muscle.
▪ Between single twitches a muscle can
completely relax.
▪ When twitches are summated the stimuli are
close together and do not allow the muscle to
relax fully.
▪ When the summation leads to unfused tetanus
the stimuli are far enough apart to allow muscle
to relax slightly between stimuli.
▪ When the summation leads to complete tetanus
the muscle reaches steady tension. Fatigue will eventually lead to loss of muscle tension despite
the continuous stimuli.
