Muscle - MPI-CBG

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Lecture 10: Muscle
11 December 2012 (Stefan Diez)
a – Skeletal Muscle
b - Cardiac Muscle
c - Smooth Muscle
Skeletal muscle has a hierarchical structure
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A muscle contains many
muscle fibers!
!
A muscle fiber is a series of
fused cells!
!
Each fiber contains a
bundle of 4-20 myofibrils!
!
Myofibrils are composed of
thin and thick myofilaments!
Each myofibril is striated !
!
!
Muscle cells can be several centimeters long!
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Myofibrils are striated
Striations - the alternation of dark and
light bands within a myofibril, produced by
the arrangement of thick and thin filaments!
dark A band
light I band
H band
Thick and thin filaments overlap to form dark A bands
Thin filaments alone form light I bands
The H band, within the A band, is where there is no overlap
The Z-line is a dark line within the I bands
Two Z-lines delimit the
unit of muscle contraction
- the Sarcomere
During muscle contraction sarcomeres shorten
... i.e. the distance between
Z-lines decreases - the
width of the H and I-bands
also decreases !
!
... the amount of overlap
between actin and myosin
increases!
!
Contraction is produced by
an interaction between actin
and myosin !
!
Through the formation of
cross bridges, the actin is
pulled into the space
between the myosin
filaments!
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relaxed
contracted
relaxed
contracted
Thick filaments are composed of myosin!
!
Thin filaments are composed of actin!
Force is generated between thick and thin filaments
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Thin Filament!
Crossbridges!
Thick filaments are composed of many myosin molecules!
!
Each myosin molecule has a protruding head!
!
Thin filaments are composed of a double helix of globular actin molecules!
!
Myosin heads form cross-bridges by interacting with the actin thin filament!
Force is generated by flexing myosin heads
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During contraction, flexing of the myosin heads pulls the thin filaments over the
thick filaments - shortening the sarcomere!
The full picture
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Muscle contraction requires ATP
Cleavage of ATP activates the
myosin head!
!
When activated, the myosin head
can form a cross-bridge to actin!
!
After binding to actin, Pi and ADP
are released from myosin head head flexes, pulling the actin
filament over myosin!
!
ATP is required to detach myosin
from actin and repeat cycle!
!
Multiple rounds of the cycle at
many myosin heads results in
shortening of the sarcomere !
The crossbridge cycle
ATP!
binding!
Pi release!
then!
ADP release!
rigor binding!
Low Duty Cycle of about 0.1
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Muscle contraction can be strong and fast
Tension is proportional to overlap!
!
Each sarcomere shortens < 1 µm
with about 5 µm/s (filament speed)!
!
Human biceps muscle (20 cm) has
80,000 sarcomeres - when each
shortens 0.25 µm, the whole
muscle shortens by 2 cm!
!
!!! Volume conservation - muscle
diameter increases !!!!
!
Biceps (without resistence)
contracts 2 cm in 100 ms, !
i.e. serial addition to 200,000 µm/s!
!
Muscle strength about 10 kg/cm2!
Muscle contraction
relaxed!
contracted!
Muscle contraction is regulated by
Muscle contraction requires Ca2+
Ca2+ presence exposes the actin
binding sites through an interaction
between Ca2+ and troponin!
!
Tropomyosin associates with actin
and blocks binding sites on actin when
Ca2+ is absent!
!
Troponin associates with tropomyosin
and causes a conformational change
in tropomyosin when Ca2+ associates
with troponin!
!
ATP is normally present in live
muscle at all times - the depletion of
ATP in dying muscle causes formation
of permanent cross-bridges the dying
muscle becomes rigid - rigor mortis !
Ca2+
Ca2+
When muscles are relaxed Ca2+
is stored in sarcoplasmic
reticulum - release causes
contraction cycle to begin!
is stored in the sarcoplasmic reticulum
The sarcoplasmic reticulum (SR) surrounds each myofibril, and is
connected to the muscle cell membrane (sarcolemma) by T-tubules!
Skeletal muscle fiber
contraction is the result of
nervous stimulation!
!
!
Nerve stimulation results in
change in permeability of the
sarcolemma and SR!
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Muscle!
Fiber!
(Cell)!
The stimulated SR membrane becomes permeable to Ca2+ - releasing
stored Ca2+ - and the contraction cycle can begin!
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Muscle contraction is triggered by nerval stimulation
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Nerves connect to muscles at neuromuscular junctions - a single nerve
may connect with more than one muscle fiber (cell)!
!
The nerve and the muscle fibers it innervates is a motor unit !
Muscle contraction is triggered by nerval stimulation
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Nerve stimulation involves the release of a neurotransmitter from the axon
terminus at the neuromuscular junction - excitation-contraction coupling !
The neurotransmitter is
Acetylcholine (ACh)!
!
ACh binds to receptor proteins
on the sarcolemma and
changes membrane
permeability - change is
transmitted (new action
potential) along membrane of
the T-tubule to the SR!
!
Ca2+ channels in the SR open
and release Ca2+ into myofibril!
Relaxation of muscle fibers involves the uptake of Ca2+ from the cytoplasm of
the muscle fiber by the SR (by ATP-driven Ca2+ pumps) within about 30 ms !
Muscle contraction is triggered by nerval stimulation
Muscle force is regulated by number of motor units
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Small force muscle contractions involve few motor units!
!
Higher force contractions involve an increased number of motor units!
There are various types of muscle fibers
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Fast-twitch fibers (type II fibers) - common in muscles that
move eyes - reach maximum tension in 7.3 msec!
!
Slow-twitch fibers (type I fibers) - common in leg muscle reach maximum tension in 100 msec!
!
!
!
!
!
Many muscles have !
a mixture of slow and !
fast- twitch fibers!
There are various types of muscle fibers
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Slow-twitch fibers are able to sustain contractions over long periods without
fatigue - use aerobic respiration, have rich vascular supply, many
mitochondria, high concentration of myoglobin -> red color, red fibers !
Fast-twitch fibers are liable to fatigue use anaerobic respiration, have
stored glycogen, have reduced vascular supply, fewer mitochondria, less
myoglobin, white fibers !
!
Muscle fatigue is associated with the build-up of lactic acid due to anaerobic
metabolism of glucose!
!
The production of lactic acid allows glycolysis to continue for short periods in
the absence of oxygen but eventually lactic acid build-up inhibits enzymes of
glycolysis!
!
Lactic acid build-up produces an oxygen debt !
!
Lactic acid must be removed from muscle by aerobic metabolism after
strenuous activity ceases!
Muscle twitches can add up
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A single brief contraction: A single impulse on motor neuron produces a
single twitch contraction followed by rapid relaxation. Increasing the
stimulation can increase the strength of a twitch up to a maximum.!
!
If two impulses are applied in rapid succession a greater state of contraction
results - second twitch adds to first - summation !
!
!
!
!
!
!
!
!
!
!
A series of rapid impulses applied at increasing frequency produces a
smooth sustained contraction - tetanus - as in normal muscle contraction.!
Cardiac/Smooth Muscle can contract spontaneously
Cardiac muscle is striated - but muscle cells are not arranged as in
skeletal muscles!
Muscle cells are branched
and connected to each other
at intercalated disks - have
gaps at disks that allow
stimulation to be quickly
passed from cell to cell.!
!
!
Stimulation begins at
pacemaker cells!
!
About 3 billion contractions
per human lifetime (similar
to car engine)!
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Cardiac/Smooth Muscle can contract spontaneously
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Smooth Muscle - surrounds hollow organs - stomach, intestine, arteries,
bladder, uterus - capable of sustained contractions!
!
Thick and thin filaments lie parallel to each other but groups are arranged
irregularly - anchored to cell membrane or dense bodies!
!
Lack SR - Ca2+ enters from extracellular fluid - Ca2+ binds calmodulin complex activates enzyme that phosphorylates myosin heads - allows crossbridge formation - variation in Ca2+ concentration varies strength of contraction!
!
Some smooth muscles do contract in response to nervous stimulation - e.g.
muscles of iris!
!
Other smooth muscles contract spontaneously - through the action of
stimulatory cells within the muscle - e.g. gut!
!
Smooth muscle is capable of contraction after extreme stretching - not true of
striated muscle!
Rigor mortis (Latin: rigor stiff , mors, mortis of death ) !
... one of the recognisable signs of death that
is caused by a chemical change in the
muscles after death, causing the limbs of the
corpse to become stiff and difficult to move or
manipulate.!
!
In humans: commences after about 3 h,
reaches max. stiffness after 12 h, and
gradually dissipates until approximately 72 h
(3 days) after death.!
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http://healthteller.blogspot.c
om/2011/02/
rigor-mortis.html
Application in forensic pathology!
The degree of rigor mortis may be
used in forensic pathology to
determine the approximate time of
death.!
After death → respiration stops → depletion of oxygen → stopped ATP production !
(a) → no Ca2+ pumping out of myofibrils → Ca2+/troponin → crossbridges!
(b) → no release of myosin from actin → crossbridges remain in rigor!
!
→ creating a perpetual state of muscular contraction, until the breakdown of
muscle tissue by digestive enzymes during decomposition.!
Rigor mortis (Latin: rigor stiff , mors, mortis of death ) !
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Applications in industry!
-  important in meat technology (onset and resolution determines tenderness)!
If the post-slaughter meat is immediately
chilled to 15°C, a phenomenon known as
cold shortening occurs, where the muscle
shrinks to a third of its original size. This will
lead to the loss of water from the meat
along with many of the vitamins, minerals,
and water soluble proteins. The loss of
water makes the meat hard.!
!
Cold shortening is caused by the release of
stored calcium ions from the sarcoplasmic
reticulum of muscle fibers in response to
the cold stimulus. The calcium ions trigger
powerful muscle contraction aided by ATP
molecules.!
That s why: Aging the meat ...!