SKELETAL MUSCLE Flashcards
describe the sarcomere
The functional unit of skeletal muscle
composed of different filament Systems:
-Thin filament system
-Thick filament system
■ A band (dark band)
> consists of a stacked set of thick (myosin) filaments
■ I band (light band)
› Consists of the array of thin (actin) filaments, and is the region where they do not overlap the thick filaments
■H zone
> The lighter area in the centre of A band where the thin filaments do not overlap with thick filaments
■M line
› Consists of anchoring proteins that hold the thick filaments together vertically within each stack
■ Z line
> Consists of anchoring proteins that hold the thin filaments together vertically within each stack
› Area between two Z lines is called a sarcomere
describe myosin filament
The myosin molecule is composed of six polypeptide chains-two heavy chains and four light chains
The two heavy chains wrap spirally around each other to form the tail of the myosin molecule. One end of each of these chains is folded bilaterally into a myosin head.
2 sites on myosine head:
- actin binding site
- myosin ATPase site
Heads form cross-bridges which interact with thin filaments actin during contraction
Each cross-bridge is flexible at hinges
describe actin filament
-composed of three protein components: F-actin, tropomyosin, & troponin.
F- Actin: The backbone of the actin filament .composed of polymerized G-actin molecules, with one molecule of ADP in any one side. (Active Site)
- tropomyosin: runs along the groove of each twisted actin filament.cover active sites on myosin at rest
Troponin: It present intermittently along the sides of the tropomyosin.
It has 3 subunits
Troponin I - has a strong affinity for actin, (inhibit )
Ttroponin T - Complexes with tropomyosin
Ttroponin C – binds with calcium ions
short note in other/associate protein function
- Actinin, which attaches actin filament to ‘Z’ line.
alpha actinin: contributes to regulating the length and tension within the stress fibers.
beta actinin: determining cell shape and controlling cell movement (motility) - Desmin, which binds ‘Z’ line with sarcolemma.
- Nebulin, which runs in close association with and parallel to actin filaments.
- Titin, a large protein connecting ‘M’ line and ‘Z’ line. Each titin molecule forms scaffolding (framework)
for sarcomere and provides elasticity to the muscle.
What Keeps the Myosin and Actin Filaments in Place?
Titin Filamentous Molecules-These springy titin molecules act as a framework that holds the myosin and actin filaments in place so that the contractile machinery of the sarcomere will work.
Sarcoplasm. fills spaces between myofibrils
- contains large quantities of potassium, magnesium, and phosphate, multiple protein enzymes.
-contains large amounts of ATP
Sarcoplasmic Reticulum
-has a special organization that is extremely important in controlling muscle contraction
-The very rapidly contracting types of muscle fibers have especially extensive sarcoplasmic reticulum
draw a neatly labelled diagram of sarcomere
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Sliding Filament theory
- Contractions that produce a shortening of the muscle cell
- thin filaments of sarcomere slide between thick filaments toward M line
- A bands move closer together but do not change in length
- Z lines move closer together
- I bands are shortened
Draw and explain the structure of neuromuscular junction (NMJ).
Skeletal muscle fibres are stimulated to contract by somatic motor neurons
An axon supplying a skeletal muscle fibbers approaches its termination, it loses its myelin sheath and divides terminal buttons
The terminal buttons contain lots of mitochondria and vesicles that contain acetylcholine
Active zones –for vesicular release of neurotransmitter
The buttons fit into junctional folds of the motor end plate
ACh diffuses across the synaptic cleft and binds with nicotinic cholinergic receptors (nAChR) on channels at the MEP
Motor End Plate(MEP)
Specialised portion of sarcolemma to which axon terminal fits numerous junctional folds to increase surface area
It contains nicotinic cholinergic receptors (nAChR) which are located on the ACh-gated cation channels
Presence of acetyl cholin-esterase (AChE)
Quantal Release of ACh
ACh is released via exocytosis in quanta
1 vesicle = 1 quantum ( ~ 10,000ACh)
1 nerve impulse stimulate release of 100 quanta (- 1million ACh)
fate of ACH
After binding with the receptor (1-2 ms after released), ACh will be hydrolysed to choline and acetate by acetylcholinesterase (AChE) Choline returns to motor nerve terminal for Ach re-synthesis
acetate :diffuses into the surrounding medium
Small amount of ACh that does not bind will be diffused out of the cleft
Formation of the EPP
*RMP of postsynaptic membrane: -80 to -90 mV
small depo- 1 quanta Ach release
-Ach diffuses into MEP
- binds to nAch receptor
- ach- gated cation channels open
- non-specific influx of Na+ and efflux of K+
- influx,efflux increase cause transient depo of membrane generating end plate potential
*But when critical level of -60mv reached triggers action potential in muscle fibre in both direction
characteristics of EPP
characteristics of MEP
Non- propagated, Does not obey All or None Law.
Local event
Graded potential
Magnitude depends on the amount and duration of Ach at the MEP
Undergoes summation
events at NMJ
1.Nerve action potential reaches axon terminal
2. this triggers opening of voltage gated Ca channels
3. Ca influx occurs and this triggers docking of synaptic vesicles and exocytosis of ACh
4. ACh diffuses across the synaptic cleft & binds with nACh R on the MEP of the muscle cell membrane
5. This binding brings about the opening of cation channels, large movement of Na+ into the muscle,smaller movement of K+ outward.
6.result in end-plate potential (EPP).
7.local current flow opens voltage-gated Na+ channels in the adjacent membrane
8.The resultant Na+ entry depolarises the potential to threshold, initiating an action potential, which is propagated throughout the muscle fibre
9. Inside the pre-synaptic knob, choline & acetyl CoA recombine to become ACh & taken back into vesicles
ACh is rapidly hydrolysed by AChE to choline + acetate
Choline is transported back into the axon terminal
Motor end-plate repolarises
docking
Docking is achieved by force-generating interactions of the vesicle membrane (VM) protein synaptobrevin with the PM proteins syntaxin and SNAP25. These interactions, which produce force by forming SNARE core complex, are regulated by auxiliary proteins
mind map of NMJ events
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Differences between Synapse and NMJ
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Differences between EPP & Action Potential
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drugs MCQ
go through skeletal muscles slide 2
Myasthenia gravis
Autoimmune disease
Body produces antibodies that destruct own motor end-plate Ach receptors, Decrease EPPs produced.
Condition characterised by extreme muscular weakness & rapid onset of fatigue
Treat with anticholinesterase (e.g.: neostigmine or physostigmine) →To decrease the activity of AChE and prevents ACh from being broken down by AChE
→ Prolong the action of ACh
Clinical Features of Myasthenia gravis
Weakness, easy fatigability of skeletal muscles
Weakness of levator palpabrae muscle
lowering of eyelid (Ocular myasthenia)
Drooping of one or both eyelids (ptosis).
Blurred or double vision (diplopia).
A change in facial expression
Difficulty in swallowing
Weakness of extraocular muscles, impairment & weakness of voice, speech, ability to chew & swallow
Generalized weakness of proximal muscles, neck support of head
Respiratory muscle weakness and shortness of breath.
What is the cause of this Cross-bridge?
Inhibition of the Actin Filament by the Troponin-Tropomyosin Complex; Activation by Calcium Ions.
Interaction Between the “Activated” Actin Filament and the Myosin Cross-Bridges—The “Walk-Along” Theory of Contraction
ATP as the Source of Energy for Contraction—Chemical Events in the Motion of the Myosin Heads
Role of Calcium
-Ca2+ released from sarcoplasmic reticulum
- Ca2+ binds to troponin C
- troponin complex changes confirmation, moves tropomyosin and exposes actin active site
Myosin head binds to actin active site, form cross-bridge, moves & produces powerful strokes
Actin slides in- muscle fibre contracts
Cross-bridge continues while Ca2+ is present
When action potential stops, Ca2+ is pumped back to SR
Tropomyosin covers back actin’s active site
Relaxation occurs
Role of ATP
-ATP hydrolysed by myosin ATPase; ADP and Pi remain attached to myosin; energy is stored within the myosin head
-Ca2+ released on excitation, removes inhibitory influence from actin →→ energised myosin head binds with actin
-Myosin bends and causes power stroke actin slides on myosin
-ADP and P, are released after power stroke is completed
-ATPase site is free for attachment of
another ATP
-Attachment of new ATP permits detachment of myosin head
-Cross-bridge cycling continues
Power stroke of myosin in skeletal muscle
A) At rest, myosin heads are bound to ADP and are said to be in a “cocked” position in relation to the thin filament, which does not have Ca2+ bound to the troponin–tropomyosin complex.
B) Ca2+ bound to the troponin–tropomyosin complex induced a conformational change in the thin filament that allows for myosin heads to cross-bridge with thin filament actin.
C) Myosin heads rotate, move the attached actin and shorten the muscle fiber, forming the power stroke.
D) At the end of the power stroke, ATP binds to a now exposed site, and causes a detachment from the actin filament.
E) ATP is hydrolyzed into ADP and inorganic phosphate (Pi) and this chemical energy is used to “re-cock” the myosin head
excitation contraction coupling
- Ach released from the terminal of a motor neuron initiates an action potential in the muscle fibres
- Muscle action potential travels down T tubule
-depo of t-tubule activates SR via dihydropyridine receptors
- influx of Ca trigger elease of Ca stored in SR by activating ryanodine receptors - Ca2+ binds to troponin, exposing actin’s
cross-bridge binding sites - Myosin head binds to active site, moves and produces power stroke
- Actin slides in, muscle fibre contracts resulting in contraction of whole muscle
- ADP and P1 are released after the power stroke is complete
- New ATP binds to myosin head; detachment of the cross bridge
- Cross-bridge action continues while Ca2+ is present
- When action potential stops, Ca2+ is pumped back to SR
- Tropomyosin covers back active sites
- Relaxation occurs
General Mechanism of Muscle Relaxation
- cholinesterase released and ACH breakdown
- Sarcolemma and T-tubules repolarized
- SR Ca2+ pump activated abd Ca2+ retuen to SR terminal cisternae
- Actin myosin crossbridge formation termination
- return of tropomyosin to actin binding site
- mg2+ complex formed with ATP
- passive sliding of filaments
- sarcomeres return to resting state
Describe the length tension relationship for skeletal muscle.
-the active tension depends on the initial fiber length or degree of overlap of actin and myosin filaments
-Minimal prestretch: overlapping of actin filaments, some cross bridges can not be formed → ↓ active tension
-Optimal prestretch: actin filaments overlap all myosin cross bridges → Max active tension
Overstretching of the resting muscle: ↓ overlap between actin and myosin →↓ active tension
No overlapping between actin and myosin filaments → No active tension
-Maximal tension can be generated when the muscle is approximately at its natural length in the body
At lengths greater or less than natural length muscle develops less tension
Mention the differences between isotonic and isometric contractions.
table in downloads
List the differences between two types of skeletal muscle fibers.
lecture notes
Explain denervation hypersensitivity.
-When a muscle loses its nerve supply, it no longer receives the contractile signals that are required to maintain normal muscle size. Therefore, atrophy begins
After about 2 months, degenerative changes begins to appear in the muscle fibers themselves. If the nerve supply to the muscle grows back rapidly, full return of function can occur in as little as 3 months, but from that time onward, the capability of functional return becomes less and less, with no further return of function after 1 to 2 years.
In the final stage of denervation atrophy, most of the muscle fibers are destroyed and replaced by fibrous and fatty tissue.
The fibrous tissue that replaces the muscle fibers during denervation atrophy also has a tendency to continue shortening for many months, which is called contracture.
-practice of physical therapy
Describe Rigor mortis.
- skeletal muscles become rigid 3 to 4 hours after death
Following death,
-[Ca2+]; begins to rise - Ca2+ permits actin bind with the myosin cross bridges, which were already charged with ATP before death
-No fresh ATP available after death, actin and myosin remain bound in rigor complex
latent period
- the delay between stimulation and the onset of contraction
smooth muscle contraction vs skeletal muscle contraction
senior ss
