Download 16 Skeletal muscle

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Skeletal Muscle Physiology
First of all, which muscle is which
- Skeletal muscle:
o
o
o
o
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Cardiac muscle:
o
o
o
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Well-developed cross-striations
Does not contract in absence of a nerve stimulus
The individual muscle fibers DO NOT connect functionally or anatomically (i.e. they don’t form a single sheet
of cells, and one fiber’s action potential wont get transmitted to the next)
Generally, skeletal muscle is under voluntary control
Also has cross-striations
Is functionally syncytial: cells are connected well enough to conduct action potentials to one another
Can contract on its own, without stimulus (but this is under some control via the autonomic nervous system,
which modulates its activity)
Smooth muscle:
o
o
Has no cross-striations
Two broad types:
 VISCERAL or “unitary” smooth muscle:
Functionally syncytial, action potentials propagate from cell to cell
Contains pacemakers which discharge irregularly, but remains under control of the
autonomic nervous system
Found in most hollow viscera
 MULTI-UNIT SMOOTH MUSCLE
Found in the eye and some other locations
Does NOT activate spontaneously
SKELETAL MUSCLE ORGANIZATION
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Each muscle is a bundle of fibers
Each fiber is a long, multinucleated single cell
Each fiber is surrounded by a SARCOLEMMA- the cell membrane
There are NO SYNCYTIAL BRIDGES between the cells. When one cell goes off, the others don’t follow.
TRANSVERSE TUBULES: T-tubules, invaginations of
the sarcolemma, they form part of the T-system; the space
inside is an extension of the extracellular space.
SARCOLEMMA: the muscle cell membrane
A single muscle fiber: one long cell, a tube of
cytoplasm with holes in it. The holes are T-tubules;
wells which lead down into the T-system. Inside, each
mucle fibre contains myofibrils which are surrounded
by sarcoplasmic reticulum. Myofibrils are separated
by mitochondria. Several nuclei float around the
place.
SARCOPLASMIC RETICULUM: internal double layer of membrane which contains calcium.
TERMINAL CISTERNS: these are enlargements of the sarcoplasmic reticulum which are in close contact with the
T-system. They are found at the junctions of the A and I bands of the myofibril.
MYOFIBRIL: the basic contractile element of a muscle cell; each is further divisible into individual filaments. The main proteins
contained therein are myosin-II, tropomyosin, troponin, and actin. The myofilaments are STRIATED.
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SKELETAL MUSCLE STRIATIONS
A, H and M are dark striations; I and Z are light.
A band: myosin
H band
M line
I band: actin
SARCOMERE:
Area between two
adjacent Z lines
A band: myosin
This pattern is produced by the orderly
arrangement of actin, myosin, and all the other
proteins.
- myosin makes up the THIN FILAMENTS,
which form the A bands
- actin makes up the THICK FILAMENTS
which form the less densely-staining
I bands
- The H-band is the area where the thick and
thin filaments don’t overlap: only relaxed
Z line
muscle has H bands
- The Z lines allow anchoring of the thin
actin filaments
- A crossection of the A band would reveal
each thick myosin filament to be
surrounded by 6 thin actin filaments in a
precise hexagonal pattern
Thin filaments: actin
myosin
Thick filaments: myosin
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each thick filament holds hundreds of myosin molecules
each myosin molecule has two globular heads 9in contact with actin) and a long tail ( all the tails meet at the M line)
the heads contain an actin-binding site and an ATP-hydrolysing site
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The thin filaments are made of helical actin molecules, with tropomyosin wrapped around them, and troponin
embedded along them.
The troponin molecule has 3 subunits:
o Troponin T binds the troponin complex to the tropomyosin
o Troponin I inihibits the interaction of myosin and actin
o Troponin C contains the calcium-binding site
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OTHER PROTEINS OF NOTE include Dystrophin:
o Dystrophin acts as a scaffold protein, connecting the myofibrils to the sarcolemma membrane. Basically, it
gives the muscle fibers their shape and strength.
o Muscular dystrophies are disorders resulting from an abnormal dystrophin architecture. The dystrophin gene
is among the largest genes in the body.
o Duchenne muscular dystrophy is caused by a complete absence of the protein
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ELECTRICAL PHENOMENA IN SKELETAL MUSCLE
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RESTING MEMBRANE POTENTIAL OF A MUSCLE CELL IS ABOUT -90mV
Action potentials are conducted along the muscle fiber at about 5 metres per second
After-polarization is relatively prolonged
INSIDE THE MUSCLE CELL: concentrations in mmol/L
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12mmol Na+
155 mmol K+
3.8 mmol Cl8 mmol HCO3155 mmol organic anions, i.e. phosphates and proteins
IN THE ECF:
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145 mmol Na+
4 mmol K+
120 mmol Cl27 mmol HCO30 mmol anionic proteins
THE EQUILIBRIUM POTENTIALS:
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Na+
+65 mV
K+
-95 mV
Cl-90mV
HCO3- - 32 mV
CONTRACTILITY IN SKELETAL MUSCLE
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A “muscle twitch” is a single action potential which causes a single contraction
The twitch happens about 2 ms after the start of membrane depolarization
FAST muscle fibers have a twitch duration as fast as 7.5 milliseconds
SLOW muscle fibers have a twitch duration about 100ms
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The contraction itself is caused by the thick and thin filaments sliding over each other
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The width of the A bands is constant; Z-lines move closer together
MECHANISM OF CONTRACTION
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At rest, tropinin I covers the site where actin and myosin interact.
At rest, the myosin heads is tightly bound to ADP
When the muscle membrane depolarizes, there is suddenly tons of Ca++ in the cytosol:
- the Ca++ binds to Troponin C
- this weakens the bond between troponin-I and actin; releasing the actin binding site
- The myosin head and the actin binding site form a cross-bridge
- When the cross-bridge is formed, ADP is released from the myosin head
- THE RELEASE OF ADP CAUSES A CONFORMATIONL CHANGE IN THE MYOSIN HEAD:
The head moves, pulling the actin filament. This is the “power stroke”.
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ATP quickly binds to the myosin head and this causes it to release the actin filament; the cross-bridge is broken
The myosin head quickly hydrolyses the ATP into ADP; this causes the head to return to normal shape, ready to
stroke again.
As long as there is enough calcium and enough\ ATP, the cycle continues
Each power stroke shortens the sarcomere by about 10 nm
Each thick filament has about 500 myosin heads, and each head cycles about 5 times per second
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EXCITATION-CONTRACTION COUPLING
Action
potential
T Tubule
Sarcoplasmic reticulum: terminal cistern
ADP
Dihydropyridine
receptor
ATP
Ryanodine
receptor
SERCA
pump
Ryanodine
receptor
Ca++
Ca++
Muscle contraction occurs because excess calcium
is pouring out of the sarcoplasmic reticulum
Myofibril
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That is the name we give to the process by which depolarization of the muscle fiber initiates contraction
The action potential travels down into the middle of the muscle fiber via the T-system
Depolarization of the T-tubule membrane causes activation of the DIHYDROPYRIDINE receptors, so named after the
drug which blocks them
 In the heart, the dihydropyridine receptor causes Ca++ release which then triggers the
ryanodine receptor (which is a calcum-gated calcium channel)
 In skeletal muscle, the dihydropyridine receptor binds directly to the ryanodine
receptor. When the action potential reaches the dihydropyridine receptor, it causes
the ryanodine receptor to open.
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The ryanodine receptor is a calcium channel, and when triggered, it causes the release of Ca++ from the terminal
cisterns of the sarcoplasmic reticulum.
This release of Ca++ triggers other ryanodine receptors and more Ca++ is released (Calcium-gated calcium release)
The excess calcium is pumped out of the cytosol back into the sarcoplasmic reticulum by the
SERCA pump (sarcoplasmic or endoplasmic reticulum calcium ATPase)
NOTE: ATP is required for actin-myosin contractions AS WELL AS for relaxation (it powers the SERCA pump)
Types of contractions
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ISOMETRIC: same length; the muscle doesn’t shorten appreciably
ISOTONIC: contraction against a constant load with decrease in muscle length
Isotonic contractions do useful work, while isometric ones don’t (because work is the product of force times distance)
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SUMMATION OF CONTRACTIONS
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The contractile mechanism does not have a refractory period; re-stimulation of an ongoing contraction will
produce another contraction on top of the existing one.
With rapidly repeated stimulation, activation of the contractile response occurs repeated before any
relaxation has occurred
This constant contraction is called a TETANIC CONTRACTION
COMPLETE TETANUS = no relaxation at all
INCOMPLETE TETANUS = periods of incomplete relaxation take place between periods of contraction
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During complete tetanus, the tension developed is about 4 times the tension of individual twitch contractions
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determined by the twitch duration of that particular muscle
if the twitch duration is 10 milliseconds, you need to stimulate the muscle MORE FREQUENTLY then every
10ms in order for summation to occur
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HOW OFTEN MUST I STIMULATE THE MUSCLE TO GET TETANUS?
MUSCLE LENGTH, TENSION, AND VELOCITY OF CONTRACTION
TOTAL TENSION = tension developed when the muscle contracts
isometrically (without changing its length)
PASSIVE TENSION = tension in unstimulated muscle
ACTIVE TENSION = actual amount of tension generated by the contractile
process
o = the difference between passive tension and total tension at a
given length
o The length of muscle at which the active tension is maximal we
call the RESTING LENGTH
o This is because In the body, most muscles achieve maximal
active tension at a normal resting length
Total tension
Active tension
Tension
This makes sense because:
o
Passive tension
Length
o
When muscle is stretched, the overlap between actin and myosin
filaments is reduced, and so there is less cross-linkages (so the
force generated is less)
When the muscle is squished to some length shorter than resting
length, there is too much overlap between actin and myosin
filaments, and thus there is less room for actin to move (less
contraction is possible)
THE VELOCITY OF MUSCLE CONTRACTION VARIES INVERSELY WITH THE LOAD ON THE MUSCLE
AT A GIVEN LOAD, THE VELOCITY IS MAXIMAL AT RESTING LENGTH, AND DECLINES IF THE MUSCLE IS SHORTER
OR LONGER
MUSCLE FIBER TYPES
o
THERE ARE 3 MAIN TYPES:
Type 1
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slow oxidative fibers
moderate SERCA activity, small diameter, slow glycolytic capacity
high OXIDATIVE capacity, more mitochondria, higher capillary density and myoglobin content
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fast oxidative and glycolytic fibers
high capacity SERCA pumps, large diameter fibers, high glycolytic capacity
high oxidative capacity
Type 2a
Type 2b
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fast glycolytic fibers
also large, also high-capacity calcium pump, also high glycolytic capacity, but much less oxidative
capacity
there are numerous different forms of myosin tropomyosin and troponin, but only one form of actin
Type 2a and 2b fibers are most susceptible to exercise- they grow fastest
Type 1 fibers are most susceptible to inactivity- they atrophy fastest
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MUSCLE METABOLISM AND ENERGY SOURCES
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MUSCLE CONTAINS PHOSPOHRYLCREATINE
This is an energy-rich compound, a short-term energy battery
It can be hydrolysed into creatine and phosphate groups with considerable energy release
At rest, ATP is used to form phosphorylcreatine from creatine
During exercise, phosphorylcreatine is hydrolysed between the heads of myosin and actin, forming
ATP out of ADP and thus permitting contraction to continue
At rest
ATP
Creatine
ADP
Phosphorylcreatine
During exercise
Creatine
ATP
ADP
Contraction
CARBOHYDRATE AND LIPID METABOLISM
- At rest or during light exercise, muscles prefer lipids
- With high intensity exercise, carbohydrates are necessary: lipids don’t break down fast enough
o At high intensity exercise, the carbohydrates involved are mainly glucose from the bloodstream and glycogen
o
stores in the muscle itself. The metabolism here is oxidative phosphorylation, and is aerobic.
If O2 supplies are insufficient (muscle contracts pumping blood out of itself, it can outstrip its own blood
supply in its demand), ANAEROBIC METABOLISM takes over and glucose is broken down into lactate
o anaerobic metabolism is bad form; lactate accumulates and the falling pH eventually has an
enzyme-inhibiting effect. Acidotic muscles simply cannot function.
o However for short periods it enables far greater exertion that would otherwise be possible
OXYGEN DEBT
o
o
After a 100metre dash, where 85% of the energy supplied was supplied anaerobically, there is a lot of lactate
in the muscle and in the bloodstream.
Afterwards, at rest, a larger than normal amount of oxygen is required:
 To remove the excess lactate
 To replace the oxygen which was taken from myoglobin stores
 To replenish the ATP stores and the phosphorylcreatine stores
RIGOR
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Complete ATP and phosphorylcreatine depletion causes RIGOR, that is to say rigidity of the muscles
Its caused by all the myosin heads attaching to actin in an abnormal fixed and resistant way
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HEAT PRODUCTION IN MUSCLE
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RESTING HEAT: external manifestation of basal metabolic processes
ACTIVATION HEAT: produced when muscle is contracting
SHORTENING HEAT: proportional in amount to the distance the muscle shortens
Following contraction, heat production continues for about 30 minutes;
This is RECOVERY HEAT
It is produced by metabolic processes which return the muscle to its pre-contraction state
EFFECTS OF DENERVATION
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Loss of innervation = loss of tonic signals (maintaining muscle tone ) = ATROPHY
Sensitivity to circulating acetylcholine increases
Fibrillations appear- fine, irregular contractions (nothing like crude gross fasciculations)
THE MOTOR UNIT
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A GIVEN MOTOR AXON INNERVATES SEVERAL MUSCLE FIBERS.
Thus, when a signal is given, ALL of these fibers with contract.
A motor neuron and its gang of muscle fibers is a MOTOR UNIT
In fine muscles, eg. hands, each motor unit contains 3-6 muscle fibers
In crude muscles, eg. quadriceps, each motor unit contains 300-600 fibers
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THE FIBERS DON’T ALL HAVE TO BE BUNCHED TOGETHER: a motor neuron might innervate several fibers in a
muscle, none of them touching
THE FIBERS ALL HAVE TO BE THE SAME KIND OF FIBERS: slow, fast etc
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CLASSIFICATION OF MOTOR UNITS:
o
o
o
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SLOW (S)
FAST and RESISTANT TO FATIGUE (FR)
FAST AND FATIGUEABLE (FF)
 S units tend to have fewer fibers, FF units tend to have huge numbers of fibers
THE SIZE PRINCIPLE: motor units are not recruited at random
o
o
o
First, Slow S units are recruited to produce controlled contraction
Then, FR units are recruited to produce increased contraction over a short period
Lastly, for maximal intensity exercise, FF units are recruited
Weirdly, if you cut the nerve to a slow unit, and splice it with a fast motor nerve, that slow muscle will become fast- the myosin
ATPase activity will increase. Thus, the activity of a motor unit depends on its innervation.
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Motor units fire ASYNCHRONOUSLY: that is to say, they don’t all contract and relax simultaneously. This produces a
smooth overall contraction of the muscle
STRENGTH OF SKELETAL MUSCLES
- 3-4KG OF TENSION PER SQUARE CENTIMETRE OF CROSS-SECTION
- Constant figure for all mammals; we are not special
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Gluteus maximus: 1200kg of tension at peak load!
If all human muscles pulled in the same direction all at once, they would produce 22 tons of tension
SLOW walking consumes as much energy as FAST walking; the most comfortable walking is a form where
the leg can swing passively through some of the step, which causes less muscular exertion. This seems to
be a rate of 80 metres per minute.
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References: Ganong Review of Medical physiology, 23rd ed, chapter 5