Physiology of Skeletal Muscle Flashcards
Physiology
Structure - Connective Tissue
3 layers - all containing the structural, tough protein, collagen and varying degrees of elastic fibres - epimysium, perimysium and endomysium.
Epimysium - surrounds the whole muscle & separates the muscle from surrounding tissues
Perimysium - divides the muscle into bundles, or fascicles, of muscle cells (several hundred to several thousand per fascicles)
Endomysium - surrounds individual muscle cells
Connective tissue from all 3 layers fuse at the ends of the
muscle to form a tendon that inserts into the bone. The connective tissue acts as
anchoring points for the contractile proteins to pull against. Blood vessels, nerves and lymphatic vessels penetrate these connective tissue layers.
Structure - Muscle FIbre
- Rich in mitochondria, supplies ATP necessary for contraction and have a well developed sarcoplasmic reticulum
- Series of regular, alternating light and dark bands running across width - striated
- Endomysium separates one muscle fiber from the next, provides a route of nerve and blood capillary access to each fiber, first mechanical link from contraction of the muscle fiber to tension ultimately on tendon and bone
Transmission of Muscle Power (explain)
Dystrophin is a connective protein that connects the actin of the myofibril to the sarcolemma, and then to the endomysium via a complex of linking proteins.
By anchoring the myofibril to the sarcolemma/endomysium, when the myofibril contracts and shortens, it transmits that tension to the sarcolemma/endomysium, so that the muscle fibre
shortens.
The myofibril must be connected to the touch endomysium. If it was only
attached to the fragile sarcolemma, the sarcolemma would be pulled apart when muscle contracts.
There is a group of genetic diseases called muscular dystrophies that results in
progressive weakening of the muscles. This is because there is a lack of the linking protein, dystrophin.
-> When the myofibrils contract they tear away from the sarcolemma and damage the muscle. Over time this progressively weakens the muscle.
Explain a Myofibril under the microscope
At higher magnification with a light microscope the main bulk of a skeletal muscle fibre can be seen to consist of a series of parallel sub-units known as myofibrils.
These contain the contractile proteins of the cell and are also alternately banded light (I
bands) and dark (A bands).
This accounts for the striated appearance of the whole cell.
There is a line (or disc) called the Z line (or disc) which runs through the centre of each I
band.
The interval between 2 adjacent Z lines is called the sarcomere and is regarded as
the contractile sub-unit of the cell.
Explain Myofilaments under the microscope
At even higher magnification it can be seen that the A and I bands of the myofibrils are formed by parallel alignments of elements known as the thick
myofilaments (these show up as the A bands) and the thin myofilaments (these form the I
bands and are attached to the Z line at one end).
These myofilaments are formed from the contractile and regulatory protein molecules that control and produce tension and shortening in the muscle. Thick and thin myofilaments normally overlap each other along most of the length of the thick myofilament although the degree of overlap changes with
changes in muscle length.
Explain Thick myofilament under microscope
This is made up of a series of myosin molecules arranged in
a regular array.
Each molecule has a double head at the end pointing away from the middle of the myofilament and this head sticks out into the space between myofilaments.
The head has binding sites for actin, and for ATP. The binding site for ATP is also enzymatically active, which it breaks down ATP to release the chemical energy which is
ultimately used to do mechanical work during muscle contraction.
Explain Thin myofilament under microscope
This is made up of at least 3 different proteins.
Actin is arranged in a double stranded helix rather like a double rope of pearls twisted about its long axis.
In the groove between the 2 strands lies the molecule tropomyosin.
At regular intervals there are also molecules of troponin which are attached to both actin and myosin.
Troponin also has binding sites for Ca2+ and is important in the regulation of contraction.
Contraction - Sliding Filaments
Rest:
- myosin heads
unattached
- active on actin site
covered
Stage 1:
- Ca2+ (released from sarcoplasmic reticulum) binds to troponin
- troponin pulls
tropomyosin
- reveals active site
on actin molecule
Stage 2:
- myosin head attaches to active site on actin
Stage 3:
- ADP + P released from myosin
head, releasing energy
- myosin head pivots, shortens
sarcomere
Stage 4:
- ATP binds to myosin head necessary to detach cross-bridge
Stage 5:
- ATP splits within myosin head
- energy captured by myosin head
- trigger ‘cocked’ ready for repeat
Rigor Mortis phenomenon (explain)
After death (2-6 hours), as there is no further respiration, production of ATP in the body tissues is stopped.
In skeletal muscle, one of the first consequences is that the calcium pumps on the
sarcoplasmic reticulum no longer pump intracellular calcium back into the SR, and calcium leaks in to the muscle cells and the concentration slowly increases.
This binds to the troponin and causes the myosin head to attach to the tropomyosin, producing the power stroke on release on the ADP and Pi and causing contractions of the skeletal muscles.
As there is no further respiration and no further production of ATP, the myosin heads remain attached and the muscles remain in a state of contraction, until enzymatic breakdown of the contractile molecules occurs sometime later (hours –days).
Length-Tension Relationship (explain)
At full resting length, overlap between actin and myosin is greatest, so probability of cross-bridging is greatest and greatest tension developed.
If the fibre stretches beyond a certain point, or shortens beyond a certain point, cross-bridging is less than optimal, and tension declines.
(NB. This is a similar mechanism that helps explain Starling’s law of the heart – more in means more out! The greater the venous return to the heart, the more the initial stretch in diastole as the heart fills, and so the harder the ventricle contracts, producing a greater cardiac output).
Energy for Contraction (explain)
For any process in the body that uses energy, that energy comes specifically from the cleaving of one or more
phosphate (Pi) molecules from the ATP molecule.
Thus all other energy stores such as carbohydrates, fats, proteins and creatine phosphate (PC), will ultimately produce ATP.
Only very small amounts of ATP are stored in muscle (or elsewhere) – enough for less
than a second of work! PC is stored in larger amounts, but still relatively small, and can
provide phosphate to re-phosphorylate the ADP back to ATP, and can sustain work for just a few seconds.
The vast majority of energy for muscular work comes from breakdown of carbohydrates, fats and, on occasions, proteins, which are stored in much greater amounts in muscle, liver, fat deposits etc., which all must produce ATP for energy
Regulation of Contraction-Excitation Contraction Coupling
Skeletal muscles remain relaxed until they are commanded to act by means of an excitory impulse down the α-motor nerve.
This results in the firing of an action potential on the muscle membrane and it is this depolarization of the muscle fibre that leads to contraction. (Depolarising the cell any other way, eg. electrically, as in the EMG practical, is equally effective at provoking contraction).
The action potential is conducted across the plasma membrane of the muscle fibre.
At regular intervals the membrane penetrates deep
into the muscle fibre forming structures known as T-tubules, so that an action potential is
rapidly conducted into regions adjacent of the centre of the fibre rather simply passing over the outermost surface.
Depolarising the membrane and T-tubules results in the release of large amounts of Ca2+ from the sarcoplasmic reticulum, which is separated from the extracellular space but is in very close contact with the membrane in the region of the T-tubules.
Cytoplasmic [Ca2+] rises acting as the intracellular signal for contraction. It binds to troponin on the thin myofilaments, causing troponin to change shape.
At rest tropomyosin blocks any binding between myosin and actin.
Once tropomyosin is moved
by Ca-troponin, cross bridge formation can proceed and contraction ensues.
After the depolarising stimulus has passed the sarcoplasmic reticulum pumps Ca2+
back out of the cytoplasm into its storage vesicles, thus reducing [Ca2+] once more.
Troponin is no longer Ca bound so tropomyosin moves back into its normal position where
it interferes with actin-myosin binding and the contraction ends.
Thus, regulation of intracellular calcium is key to initiating and stopping contraction.
Properties of Contracting Muscle
When muscle receives repeated stimulation at a frequency such that the muscle cannot completely relax from the previous stimulation before the next one arrives, tension
produced adds up (summates) to a lager value than the single stimulus.
When repeated shocks are delivered at above a certain frequency (30/sec for slow muscle, 120/sec for fast muscle) the response fuses into a smooth contraction with much greater tension compared to the single twitch.
This is TETANUS, and is due to the accumulation of calcium ions released by the SR with repeated stimulation allowing maximal cross-bridging
in the muscle fibre.
Fibre Types Properties - Fast Fibres (type IIb, fast glycolytic)
- Large fibers
- Extensive sarcoplasmic reticulum
- Large amounts of glycolytic enzymes
- Less extensive blood supply
- Fewer mitochondria
- White colour
Fibre Types Properties - Slow Twitch Fibres (type 1, slow oxidative)
- Smaller fibers
- innervated by smaller nerve fibers
- More extensive blood vessel system and capillaries
- increased numbers of mitochondria
- large amounts of myoglobin
- Red colour
