Muscle: enables movement possible
Voluntary type: skeletal muscle (you can move
your arms and legs or fingers by will)
Involuntary types: cardiac muscle (heart
pumping) and smooth muscle (gut, blood
vessels, urinary bladder etc). These muscles
move without your will and conciousness. But
neural activities (mood, fight/flight, calmness)
will change the activities of these muscles
Striations or not
Striated
Non-striated
Skeletal
muscle
Cardiac
muscle
Smooth
muscle
• The sliding filament mechanism, in which myosin filaments
bind to and move actin filaments, is the basis for shortening
of stimulated skeletal, smooth, and cardiac muscles.
• In all three types of muscle, myosin and actin interactions are
regulated by the availability of calcium ions.
• Changes in the membrane potential of muscles are linked
to internal changes in calcium release (and contraction).
Skeletal muscle
• A single skeletal muscle cell is called a muscle fiber
• Each muscle fiber is formed during development by
the fusion of a number of undifferentiated,
mononucleated cells, known as myoblasts, into a
single cylindrical multinucleated cell.
• The term muscle = a number of muscle fibers bound
together by connective tissue. Muscles are attached to
bones by tendons
The sarcomere is composed of:
thick filaments called myosin, anchored
in place by titin fibers, and
thin filaments called actin, anchored to
Z-lines .
A cross section through a sarcomere shows that:
• each myosin can interact with 6 actin filaments, and
• each actin can interact with 3 myosin filaments.
Sarcomere structures in an electron micrograph.
• Contraction refers to force generation in the
muscle fibers, not necessarily means
shortening.
• Example, holding a heavy book with your
arms straight requires muscle contraction but
not shortening (isometric contraction)
• But if you move the heavy book upward, it
involves shortening (isotonic contraction)
Contraction
involving
shortening:
myosin binds to
actin, and slides
it, pulling the
Z-lines closer
together, and
reducing the
width of the
I-bands.
Note that filament
lengths have not
changed.
Contraction:
myosin’s cross-bridges bind to actin;
the crossbridges then flex to slide actin.
The thick filament called myosin is actually a
polymer of myosin molecules, each of which
has a flexible cross-bridge that binds ATP and actin.
If Ca present, cycle
repeats.
3,4 are distinct
steps!
In relaxed skeletal muscle, tropomyosin blocks the cross-bridge
binding site on actin.
Contraction occurs when calcium ions bind to troponin; this complex
then pulls tropomyosin away from the cross-bridge binding site.
The latent period between excitation and development
of tension in a skeletal muscle includes the time
needed to release Ca++ from sarcoplasmic reticulum,
move tropomyosin, and cycle the cross-bridges.
The transverse tubules bring
action potentials into the
interior of the skeletal muscle
fibers, so that the wave of
depolarization passes close
to the sarcoplasmic reticulum,
stimulating the release of
calcium ions.
The extensive meshwork
of sarcoplasmic reticulum
assures that when it
releases calcium ions
they can readily diffuse
to all of the troponin sites.
Passage of an action
potential along the
transverse tubule. Note
that TT is very close to
SR. Depolarization is
sensed by DHP receptor,
which opens the
coupled voltage-gated
calcium channels, the
“ryanodine receptor,”
located on the
sarcoplasmic
reticulum, and calcium
ions released into the
cytosol bind to troponin.
Note that after
excitation, Ca is pumped
back to SR.
Nerve cells that innervte skeletal
muscle fibers are called motor
neurons.
A single motor unit consists of
a motor neuron and all of the
muscle fibers it controls.
The neuromuscular
junction is the point of
synaptic contact
between the axon
terminal of a motor
neuron and the muscle
fiber it controls.
Action potentials in the
motor neuron cause
acetylcholine release
into the neuromuscular
junction.
Muscle contraction
follows the delivery
of acetylcholine to the
muscle fiber.
Mechanical response of a single muscle fiber to a single action potential is
called a twitch.
iso = same
tonic = tension
metric = length
In isotonic contraction,
latent period is
considerably longer, as
shortening will not occur
until muscle tension > load
* Before shortening is
isometric contraction
Heavier load, longer latent
period
*
Contraction is isometric
when load is too heavy
All three are isotonic contractions.
Light loads are more rapidly moved than heavy loads.
T e m p o r a l s u m m a t i o n.
Complete dissipation
of elastic tension
between subsequent
stimuli.
S3 occurred prior to
the complete dissipation
of elastic tension from S2.
S3 occurred prior to
the dissipation of ANY
elastic tension from S2.
Unfused tetanus:
partial dissipation of
elastic tension between
subsequent stimuli.
Here continuous stimulation constantly
releases Ca so Ca is not effectively
pumped back to SR, resulting in prolonged
Ca elevation
Fused tetanus:
no time for dissipation
of elastic tension between
rapidly recurring stimuli.
Short sarcomere:
actin filaments
lack room to slide,
so little tension can
be developed.
Optimal-length
sarcomere: lots of actinmyosin overlap and
plenty of room to slide.
Relaxed skeletal
muscle fibers are
near lo
Long sarcomere:
actin and myosin
do not overlap
much, so little
tension can be
developed.
At rest, muscle fibers build up creatine phosphate as sources of ATP: initial
reserve for a few seconds. Later on resort to glycolysis and oxidative
phosphorylation. When muscular activities is prolonged and intense,
anaerobic glycolysis begins to provide major source of ATP with the
generation of lactic acid. Also, oxygen debt has to be repaid to metabolize
lactic acid and to regenerate creatine phosphate and ATP.
In skeletal muscle,
repetitive stimulation
leads to fatigue,
evident as
reduced tension.
Rest overcomes
fatigue, but fatigue
will reoccur sooner
if inadequate recovery
time passes.
3 mechanisms may account for the fatigue:
Accumulation of K ions in the T tubules during repolarization
Lactic acid (acidity) inhibits contractile machineries eg. Actin/myosin, Ca
release channels
ADP and Pi inhibits cross-bridge cycling.
3 major types of skeletal muscles
Slow-oxidative skeletal muscle
responds well to repetitive stimulation
without becoming fatigued; muscles
of body posture are examples. Low
myosin ATPase activities and high
oxidative capacity.
Fast-oxidative skeletal muscle
responds quickly and to repetitive
stimulation without becoming fatigued;
muscles used in walking are examples.
High myosin ATPase activities and high
oxidative capacity.
Fast-glycolytic skeletal muscle is used
for quick bursts of strong activation,
such as muscles used to jump or to run
a short sprint. High myosin ATPase
activities and high glycolytic capacity.
Most skeletal muscles include all three types.
Fast glycolytic fibers are larger in diameter and are
therefore more forceful. However, easily fatigued. Good
for “explosive”sports like high jumping or sprint.
All three types of
muscle fibers
are represented
in a typical
skeletal muscle,
Fastglycolytic
and, under tetanic
stimulation,
make the predicted
contributions to
the development
of muscle tension.
Fast-oxidative
In increasing
muscle strength, Recruitment of small motor neurons first (they activate
Slow-oxidative
slow-oxid. Fibers) and finally large motor neurons (they activate fast glycolytic fibers).
For delicate movements (eye and hand muscles), about 13 fibers
innervated by a motor neuron. For leg muscles, hundreds to thousands
of fibers in a motor unit.
Exercise or NOT
• Denervation atrophy: when the innervating neuron or
neuromuscular junctions is destroyed or non-functional,
muscle receive no stimulation and will become smaller
in diameter and will have less contractile proteins.
• Disuse atrophy: atrophy happens when a muscle is not
used for a long time.
• Exercise causes hypertrophy and enhanced ATP
production capacity.
• Remember, in atrophy or hypertrophy, no change in
muscle fiber number, but in SIZE, and metobolic
capacity.
Clincal cases of muscle abnormalities
• Muscle cramps: involuntary tetanic contraction.
Overexercise may cause electrolyte imbalance in the
extracellular fluid surrounding muscle and nerve.
These cause abnormally high neuron firing rate.
• Hypocalcemic tetany: involuntary tetanic
contraction as extracellular Ca concentration drops
to 40% of normal value. This condition increases
membrane excitability (Na influx)
Clincal cases of muscle abnormalities
• Muscular dystrophy: a protein called dystrophin
is missing. It is similar to cytoskeletal protein,
maintaining plasma membrane and cell
structural integrity. Progressive degeneration of
skeletal and cardiac muscles, eventually early
death before 20.
• Myasthenia gravis: muscle fatigue and weakness
due to destruction of nicotinic Ach receptor of
motor end plate. Reason: auto-antibodies to the
receptors. Reduced end-plate potential.
Duchenne muscular dystrophy weakens
the hip and trunk muscles, thus altering the
lever-system relationships of the muscles
and bones that are used to stand up.
Smooth muscle
• Innervated by automomic nervous system,
therefore involuntary
• Actin-myosin contractile machineries, but
organisation and excitation-contraction coupling
is different from skeletal muscle.
Thick (myosin-based)
and thin (actin-based)
filaments, biochemically
similar to those in
skeletal muscle fibers,
interact to cause
smooth muscle
contraction. Troponin
is ABSENT in SMC.
Ca binds to calmodulin (CM)
and then activates myosin
light chain kinase (MLCK)
MLCK phosphorylates
globular head of MLC. The
latter binds to actin and
slides.
Myosin ATPase has a very
low rate, therefore
contraction velocity is much
slower than skeletal muscle.
Note another ATP molecule
is to detach myosin from
actin, and its hydrolysis reenergizes the myosin head.
1
2
Sources of calcium very
different:
3
1.
Opening of voltagedependent Ca channel
2.
RACC
3.
Second messengertriggered Ca release
Some SMC are pacemaker cells
Rhythmic changes in the membrane potential of
smooth muscles results in rhythmic patterns of
action potentials and therefore rhythmic contraction;
in the gut, neighboring cells use gap junctions to
further coordinate these rhythmic contractions.
Neuronal and hormonal influences
• Some neurotransmitters increase, while some other
decrease, SMC contractility
• The same neurotransmitter can produce opposite
effects in different types of SMC: eg. Noradrenaline
contracts most SMC by acting on alpha- adrenergic
receptors, but relaxes airway SMC by acting on beta2 adrenergic receptors.
• Hormones, in a similar manner, may either stimulate
or inhibit SMC contraction.
Other factors
• Local factors will also affect SMC contractility to
tell the cell’s immediate environment. Nitric
oxide released from endothelial cells relaxes
SMC.
• Stretch opens mechanosensitive ion channels
which then cause membrane depolarization.