Lec 15: Muscle Contraction Flashcards
(84 cards)
1
Q
Muscle general functions: (4)
A
- ) Contraction
- ) Generation of force
3.) Production of movement
All types have contractile proteins (actin & myosin)
2
Q
3 Types of Muscle: (3)
voluntary?
striated?
A
- ) Skeletal: voluntary, striated
- ) Cardiac: involuntary, striated
- ) Smooth: involuntary, non-striated
3
Q
Skeletal Muscle is approximately __% od body mass and is the…
A
40-50%
largest structural component in the body)
4
Q
Skeletal Muscle function =
…many exceptions =
A
= Movement of the skeletal system
= tongue (lingual muscle), pharynx, esophagus, vocalis, diaphragm, extraocular muscles, facial muscles….
5
Q
Skeletal muscle is generally…
A
attached to the skeletal system via tendons (many exceptions)
6
Q
2 Types of tendons:
A
- Tendon of origin (bone fixed in place, towards midline)
- Tendon of insertion (moveable bone, towards periphery)
7
Q
Muscle cells =
A
muscle fibers = myofibers
8
Q
(Muscles Cells)
- shape =
- Typically, myofibers arranged in…
- Whole muscles have…
A
- long cylindrical-like cells
- …parallel
- …myofibers arranged in various patterns:
parallel, pennate, bipennate, multipennate, radiate,…
9
Q
Although we consider muscle as a
A
tissue, each muscle is an organ (a collection of tissues)
10
Q
(Skeletal muscle)
CT Components =
A
= (Allow for blood vessels and nerves to enter the whole muscle)
11
Q
Epimysium =
A
= Outer connective tissue covering
12
Q
Perimysium =
A
= Surrounds a fascicle (group of myofibers)
13
Q
Endomysium =
A
= Surrounds a myofiber
14
Q
(Skeletal Muscle Anatomy) (Longitudinal-section (whole muscle) Dark band = Light band = Myofibers are...
A
= A band
= I band
…mutlinucleated
15
Q
(Skeletal Muscle Fibers)
1.) shape =
- ) they are…
- ) Located at…
- ) t.f. we call it…
- ) Packed with…
- ) Each one contains…
- ) Responsible for…
- ) Usually, each fiber has a…
A
- ) = Long Cylindrical-like Cells (up to 1 cm in length)
- ) multinucleated = hundreds to thousands of myonuclei
- ) periphery of fiber (just within the cell membrane)
- ) “True syncitium”
- ) long cylindrical structures: myofibrils (~1 mm diam.)
- ) contractile proteins (filaments)
- ) cross striation pattern
- ) single neural connection (neuromuscular junction = NMJ is a chemical synapse)
16
Q
Sarcolemma =
A
= cell membrane of muscle cell
17
Q
Sarcoplasm (myoplasm) =
A
= cytoplasm of muscle cell
18
Q
Sarcoplasmic reticulum (SR) =
A
= modified ER of muscle cell (stores Ca2+)
19
Q
T-tubule (transverse tubule) =
A
= long tubular invaginations of/extensions from the sarcolemma and penetrate into the fiber and communicate with the SR
20
Q
Each myofibril is surrounded by the…
A
…sarcoplasmic reticulum (SR) (light blue)
21
Q
Triad =
A
= region where one T-tubule meets 2 SR (one on either side)
22
Q
Myoplasm contains…
A
mitochondria, ribosomes, glycogen, enzymes, etc.…
23
Q
Myofibril =
A
Long cylindrical proteinaceous structures (span the length of the fiber) (~1 mm in diameter) (many per fiber)
24
Q
Myofibrils contain
A
the contractile proteins (actin & myosin)
25
Myofibrils consists of...
Gives rise to...
...alternating & overlapping protein filaments in the form of repeating subunits known as sarcomeres (thousands per myofibril)
...the cross-striations (banding pattern, A and I bands)
26
Sarcomere =
= Functional unit of a muscle fiber (where contraction/force generation occurs)
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(Sarcomeres)
* *DRAW SARCOMERE**
1. ) Extends from
2. ) Thin filaments attached to
3. ) Thick filaments in
4. ) Area without thick filaments =
5. ) Thick and thin filaments
6. ) Region of no overlap in the middle of the A-band =
7. ) M-line is in...
1. ) z-line to z-line (z-disk)
2. ) z-lines
3. ) the middle (A-band)
4. ) = I band
5. ) overlap in the A-band
6. ) = H-zone
7. ) the middle of H-zone
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Thick filament contains...
Thin filament contains...
...myosin (molecular motor of muscle)
...actin (binds to myosin) & regulatory proteins (troponin & tropomyosin)
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1. ) Z-line (disc):
2. ) I-band:
3. ) A-band:
4. ) H-zone:
5. ) M-line:
6. ) Triad:
1. ) Z = Zwischen (German for “in between”, “inter”)
2. ) I = Isotropic (reflects polarized light equally in all directions) (appears light in dye stained tissue)
3. ) A = anisotropic (reflects polarized light non-uniformly) (appears dark in dye stained tissue)
4. ) H = Heller (German for “clearer or brighter”)
5. ) M = Mittel (German for “middle”)
6. ) region where t-tubule interacts with 2 regions of SR (see red circle, also see slide 9)
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Physiological contraction occurs when
thick and thin filaments interact, in response to elevated myoplasmic Ca2+ (released from SR) following an action potential.
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Hierarchical Structure of Skeletal muscle
- Whole Muscle (Organ)
- Myofiber (Cell)
- Myofibril (Subcellular structure)
- Myofilaments
- Thick filaments
- Thin filaments
- Individual proteins (Macromolecules)
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Proteins Associated with Sarcomere: (5)
1. ) Thick filament:
2. ) Thin filament:
3. ) Z-line:
4. ) M-line:
5. ) ...
1. ) Myosin (heavy and light chains), C-protein (myosin binding protein C).
2. ) actin, troponin, tropomyosin, tropomodulin, nebulin.
3. ) desmin, alpha-actinin, CapZ, several others.
4. ) M-line creatine kinase, M-line protein, myomesin, obscurin.
5. ) Others
33
Thick Filaments are primarily composed of
Myosin = ~470 kDa (big) protein = molecular motor of muscle
| The molecular motor protein of muscle (Class II myosin)
34
Myosin molecule is a...
with: (2)
...hexamer (6 protein subunits)
1.) 2 Myosin heavy chains (MyHC or MHC) (200 kDa each)
2.) 4 Myosin light chains (MyLC or MLC) (15-25 kDa each)
(2 essential + 2 regulatory)
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Each Myosin Heavy Chain has: (2)
Rod domain
| Globular Head
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Myosin Globular Head Functions: (2)
ATP binding site
| Actin binding site
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Myosin Head is found on
the heavy chain
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Myosin Head (on heavy chain) functions: (3)
1. ) ATPase activity: chemical breakdown of ATP into ADP + Pi (inorganic phosphate)
- ATP binding site
2. ) Ability to transduce chemical energy into mechanical energy
- Chemical energy released from ATP hydrolysis causes conformation change (kinetic energy)
3. ) Actin binding domain
- Binding of the myosin head to actin also causes a conformation change
39
Thick filament is formed by
many myosin molecules assembling into a filamentous structure in a “parallel” and “anti-parallel” arrangement.
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(Thin Filament)
| 2 types of actin in it:
1. ) g-actin = globular actin
| 2. ) f-actin = filamentous actin - formed by many g-actin molecules polymerizing into a long helical chain.
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(Thin Filament)
1.) The core of the thin filament is composed of...
2. ) Wrapping around the actin double helix are...
3. ) _________ blocks the site on actin to which...
4. ) At regular intervals (~ every 6 - 8 g-actins) a...
1. ) 2 f-actin helices intertwined to form a double helix.
2. ) 2 helices of tropomyosin.
3. ) Tropomyosin blocks the site on actin to which the myosin head can bind.
4. ) globular protein known as troponin is bound to tropomyosin and actin
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(Tropomyosin)
1.) shape =
2. ) Binds to
3. ) Blocks...
4. ) Each molecule spans
5. ) Forms a...
6. ) Two double helical structures per thin filament (one for...
1. ) rod like protein
2. ) actin
3. ) the site on actin to which the myosin head can bind
4. ) ~7 g-actin units
5. ) continuous double helical structure
6. ) each of the globular-actin helices)
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Troponin (TN) 3 subunits:
1. ) TN-I
2. ) TN-C
3. ) TN-T
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TN-I =
function:
= Inhibitory subunit (loosely binds with actin)
= Holds troponin to the actin filament
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TN-C =
contains...
Upon binding...
This is the...
= Ca2+ binding subunit
...Four EF-hand structures (Ca2+ binding domains)
...Ca2+ will undergo a conformational change
...“Switch” that initiates force development
46
TN-T =
Binds...
Helps to...
= Tropomyosin binding subunit
...the troponin to tropomyosin
...position tropomyosin (allowing tropomyosin to block the site on actin to which myosin can bind)
47
Skeletal Muscle Contraction Phases: (8)
1. ) Excitation (initiated at NMJ; action potential at sarcolemma & T-tubule)
2. ) Excitation-Contraction coupling (T-tubule, sarcoplasmic reticulum, Ca2+)
3. ) Active Site Exposure, or Ca2+ activation (thin filament)
4. ) Cross-Bridge Formation (thick and thin filament)
5. ) Power Stroke (myosin)
6. ) Cross-Bridge Detachment (thick and thin filaments, ATP binding)
7. ) Myosin Reactivation (myosin, ATP hydrolysis)
8. ) Relaxation (parvalbumin, sarcoplasmic reticulum)
48
(Skeletal Muscle Contraction Phases)
Sliding Filaments due to...
...results in...
...the Cross-Bridge Cycle (steps 4 – 7 repeated)
...the sliding of filaments (shortening of the sarcomere); hence the Sliding Filament Theory of Contraction
49
(1. Fiber Excitation)
1. ) Muscle is an...
2. ) Has the capacity to...
3. ) The __ is initiated at
4. ) The _________ is the pre-synaptic cell.
5. ) The _____ ______ is the post-synaptic cell.
6. ) __________ is the neurotransmitter
7. ) The ____ receptor is a...
8. ) What would happen when Acetylcholine is released at the synapse?
1. ) ‘excitable’ tissue
2. ) fire an action potential (AP)
3. ) AP is initiated at the neuromuscular junction (NMJ) (nerve-muscle synapse)
4. ) a-motoneuron
5. ) muscle fiber
6. ) Acetylcholine (Ach)
7. ) nAch receptor is a ligand-gated Na+ channel
8. ) will diffuse across synaptic cleft, bind to receptor, and if its a ligand gate Na+ channel, it will increase movement of Na+ into the cell, t.f. depolarizing the cell
50
(Basic NMJ Function)
| 1.) AP in presynaptic cell (a-motor neuron) initiates...
the release of acetylcholine (Ach, neurotransmitter) from synaptic vesicles into the synaptic cleft (at presynaptic membrane of terminal bulb).
51
(Basic NMJ Function)
| 2.) Ach will...
diffuses across the cleft and binds to its receptor (nAch Receptor) on the postsynaptic cell membrane (muscle fiber).
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(Basic NMJ Function)
| 3.) The Ach receptor (nAchR): is a
ligand – gated Na+ Channel.
53
(Basic NMJ Function)
| 4.) When bound to Ach, the
nAchR Na+ Channels open, initiating a depolarization (EPSP)
54
(Basic NMJ Function)
| 5.) The depolarization is almost always
sufficient to cause an AP.
55
(NMJ Summary of events)
1.) Action potential in
2. ) Action potential causes
3. ) Ca2+ diffuses into
4. ) Release of
5. ) Diffusion of
6. ) Ach binds to
7. ) Opening of
8. ) Depolarization of
9. ) Depolarization leads to
10. ) The AP occurs along
11. ) Results in
1. ) alpha-motoneuron
2. ) voltage-gated Ca2+ channels to open in the axon terminal
3. ) axon terminal and by interacting with the vesicles causes them to fuse with the presynaptic membrane
4. ) Ach into synaptic cleft
5. ) Ach to muscle fiber membrane
6. ) Ach receptor
7. ) Na+ channel
8. ) muscle fiber
9. ) an action potential in muscle fiber.
10. ) the entire sarcolemma and t-tubule membranes.
11. ) Activation & then contraction of the fiber
56
A. If neuron stimulation continues, the fiber will undergo...
- which =
B. When nerve stimulation stops...
which =
...a series of action potentials.
= Sustained Contraction
...acetylcholinesterase (in the synaptic cleft) will cause the hydrolysis (breakdown) of Ach into acetate and choline
= Allows for Relaxation
57
(2. Excitation-Contraction Coupling (E-C coupling))
Is initiated by...
Results in...
At rest, [Ca2+] in the myoplasm is typically =
During a contraction [Ca2+] can rise to =
Thus, [Ca2+] in the myoplasm can increase from...
This calcium transient can occur in...
...the action potential in the T-tubules
...an elevated Ca2+ in the (myoplasm)
= ~50 - 100 nM
= ~1-20 mM
...20 to 400X
...~2-5 ms
58
(E-C Coupling)
The increase in [Ca2+] in the myoplasm acts as...
E-C coupling =
Occurs at...
...a switch to ‘turn on’ muscle contraction
= coupling between the action potential in the T-tubule and the release of Ca2+ from the SR.
...the Triad: T-tubule & SR
59
Sarcoplasmic Reticulum Ca2+
At rest, total Ca2+ in the SR =
Free [Ca2+] inside the SR is =
Creates a...
Source for...
= 40,000x the [Ca2+] in the myoplasm.
= ~200 mM (~4,000 x myoplasmic [Ca2+])
...huge gradient for Ca2+ diffusion from SR to myoplasm
...the elevated myoplasmic Ca2+ is the SR Ca2+
60
(How is calcium release from the SR signaled?)
Involves 2 proteins:
& which =
1. ) Dihydropyridine receptor (DHPR) = voltage sensor
| 2. ) Ryanodine receptor (RYR) = Ca2+ release channel
61
(How is calcium release from the SR signaled?)
1.) Dihydropyridine receptor (DHPR) =
Size =
Senses...
Located in...
= voltage sensor
= Large (400 kDa) protein
...the action potential
...the t-tubule membrane
62
(How is calcium release from the SR signaled?)
2.) Ryanodine receptor (RYR) =
Size?
_ protein subunits (560,000 kDa each) protein complex =
Located in...
Appears to...
Mechanical linkage between...
= Ca2+ release channel
= Huge protein complex (over 2,000,000 kDa);
4, = SR foot protein
...the SR membrane & spans across to the t-tubule
...anchor (attach) the t-tubule to the SR at the triad
the Ryanodine receptor and the DHP receptor
63
(3. Active Site Exposure (or Ca2+ Activation, or ___ Filament Activation))
1. ) Occurs at
2. ) Myoplasmic Ca2+ binds to
3. ) Causes
4. ) Exposes
5. ) Allows for
6. ) At rest...
7. ) At initiation of contraction...
1. ) the thin filament
2. ) TN-C
3. ) a conformational change in TN and movement of tropomyosin
4. ) the binding site on actin (1 on each g-actin in the chain) for the myosin head
5. ) the myosin head to automatically bind to actin and form the Cross Bridge (strong binding state, or rigor state) between thick and thin filaments
6. ) Thick and Thin filaments are unbound
7. ) Thick and Thin filaments are bound via the myosin head = Cross-Bridge
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(4. Cross-Bridge Cycle)
| A.) At rest: (2)
1. ) Low Ca2+ in myoplasm
| 2. ) No cross-bridges
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(4. Cross-Bridge Cycle)
| B.) Active-Site Exposure: (4)
1. ) High Ca2+ in myoplasm
2. ) Ca2+ binds to troponin-C
3. ) Causes tropomyosin to move
4. ) Allows cross-bridge to form
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(4. Cross-Bridge Cycle)
| C.) Cross-Bridges form: (2)
1. ) High Ca2+ in myoplasm
| 2. ) ADP and Pi still bound to myosin head
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(4. Cross-Bridge Cycle)
D.) After the Cross-Bridges form: (3)
this is called =
& 2 things happen:
1. ) Pi is released
2. ) Myosin head swivels
3. ) Pulls actin relative to myosin
= The Power Stroke
1. ) ADP is released
2. ) Myosin remains bound to actin
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(4. Cross-Bridge Cycle)
| E. Cross-bridge detachment =
ATP binds the myosin head & causes Cross-Bridge Detachment
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(4. Cross-Bridge Cycle)
Myosin Reactivation
ATP is...
& causes: (2)
In essence, energy from ATP is...
__ _____ ____ uses up that energy
...hydrolyzed by the myosin head
1. ) The myosin head to swivel back to the original position
2. ) Myosin Reactivation
...transferred to the myosin head in the form of potential energy for movement
= The power stroke uses up that energy
70
(4. Cross-Bridge Cycle Summary)
1. ) Following Ca2+ activation...
2. ) Automatically...
- which =
- Then...
- Also at the same time...
- NOTE =
1.) the myosin head is bound to actin (Cross-Bridge Formation). ADP and Pi are bound to the myosin head.
2. ) ...the Pi is released, after which the myosin head then swivels (~45o)
- = The Power Stroke
- ...ADP is released.
- ... since the myosin head is attached to the thin filament, it pulls (slides) the thin filament relative to its position a distance of ~ 6 nm.
- = The power stroke does not directly require ATP hydrolysis
71
The power stroke does not directly require
ATP hydrolysis
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(4. Cross-Bridge Cycle Summary)
3. ) An ATP molecule will then...
- This =
4. ) The ATP molecule is then...
- This =
5. ) Once the myosin head is moved back to its original position, it will...
6. ) Provided that myoplasmic Ca2+ remains elevated...
3. ) bind to the myosin head. This causes the Cross-Bridge to break (“weak binding state”)
- = Cross-Bridge Detachment
4. ) hydrolyzed to ADP and Pi (which remain bound to the myosin head). The energy released from the hydrolysis of ATP is then used to reposition the myosin head back to its original place
- = Myosin Reactivation
5. ) automatically reform the Strong Binding State (Cross-Bridge Formation).
6. ) the cycle of events will continue and the sarcomere will shorten
73
Immediately following cross-bridge formation: (7)
1. ) Pi is released
2. ) Power Stroke occurs
3. ) ADP is released
4. ) ATP then binds
5. ) Cross-bridge detaches
6. ) ATP is hydrolyzed
7. ) Myosin is reactivated
74
(The Sliding-Filament Model)
Proposed in...
According to the model...
The movements and forces produced by...
...causes...
...1954
...muscle contraction is due to thin filaments sliding past thick filaments, with no change in length of either
...the myosin heads along the thin filament ...
...the thin filaments to move (slide) relative to the thick filament
75
The sliding of the filaments causes
the sarcomeres to shorten and generate force
76
(Muscle Force Production)
| What produces the force?
The sliding of filaments, caused by cross-bridges
77
(Muscle Force Production)
Do all contractions involve shortening of a muscle (or muscle fiber)?
& 3 types of contractions:
All of these are...
No
1. ) Concentric contractions – fiber shortens
2. ) Isometric contractions – no length change
3. ) Eccentric contractions – fiber lengthens
...normal
78
(Muscle Relaxation)
Involves the...
2 specialized proteins:
...removal of Ca2+ from the myoplasm
1.) Sarco(endo)plasmic reticulum Ca2+ ATPase pump (SERCA)
2.) Parvalbumin
Ca2+-Binding protein in the myoplasm of fast fibers
79
(1. Sarco(endo)plasmic reticulum Ca2+ ATPase pump (SERCA))
Located in...
Pumps...
...the SR membrane
| ...Ca2+ into the SR against a concentration gradient (Active Transport)
80
(Muscle Relaxation)
| 4 Steps:
1. ) Stop excitation (at neuron)
2. ) Ca2+ released from TN-C
3. ) Parvalbumin binds up the Ca2+ (might act as a shuttle)
4.) SERCA pumps the Ca2+ back into the SR
(~1/3rd of muscles energy usage is via the SERCA pump)
81
(Rigor Mortis)
| Rigor =
= the state when the myosin head is still tightly bound to actin after the power stroke and before a new ATP comes in to cause cross bridge detachment
82
(Rigor Mortis)
| Rigor Mortis =
Shortly after death, muscles become rigid (hence, the term “stiff”).
83
(Rigor Mortis)
Why does the muscle become rigid after death? =
& 6 Steps:
= Due to Ca2+ and lack of ATP.
1. ) Lack of ATP (ATP synthesis eventually stops after death)
2. ) SR pumps stop
3. ) Ca2+ leaks out of SR
4. ) Formation of cross-bridges
5. ) Not broken because no ATP to bind to cause cross-bridge detachment
6. ) Muscles are maintained in “rigor state” and become stiff
84
(Rigor Mortis)
Begins =
and lasts =
= ~2-3 hours after death
= ~72 hours
