Skeletal Muscle - Contraction Flashcards
Put the following in the correct order:
Myofiber
Myofilaments
Thin/thick filaments
Myofibril
Myofiber -> Myofibril -> Myofilaments -> Thin/Thick Filaments
What are sarcomeres?
repeating units of myofilaments found in myofibril
Describe the structure of a sarcomere
half I band - full A band - half I band
starts at a Z line and ends at a Z line
What is a Z line?
Z line runs down the middle of an I-band
What is an M line?
M line runs down the middle of an A-band
Describe the I-band
- paler
- has a very thick dark Z line
- made of thin filaments
Describe the A band
- M line
- thick filaments
- darker
What makes up thin filaments in the sarcomere?
made of twisted strands of actin and other proteins
What is actin? What is F-actin?
protein organized in a double-helical fibre that make up thin filaments
F-actin / filamentous actin is a twisted strand of composed of two rows of individual molecules of G-actin (globular actin).
What is actinin?
protein found at the Z-line of the I-band
- interconnects the thin filaments at the Z line
What is tropomyosin?
- strands of tropomyosin cover the active sites on G-actin and prevent actin-myosin interactions
- wrap around the actin helix
- coiled/double-stranded protein that is bound to one molecule of troponin midway along its length
What are thick filaments made of?
Myosin protein
- each myosin monomer has a mobile head and neck that can bind actin
Which part of the thick filament binds to actin?
Free head of the myosin monomer
- head binds to actin
- bundled in such a way that their heads are spaced out
Which part of the myosin monomer moves the head?
Hinge
- makes the head move back and forth
What is the purpose of the myosin tail?
Binds everything together - 300 myosin monomers make up each thick fibre
Interactions between ________ and ___________ make muscles move
myosin and actin
When a muscle contracts, the thin and thick filaments __________ past each other
SLIDE
What is titin on the myosin monomer?
Titin is a spring that ensures that thick filaments do not get completely out of line
What happens during contraction?
- no individual proteins are getting smaller/shorter
- they are just sliding past each other
- each sarcomere gets shorter (Decreases in length BUT THE PROTEINS THEMSELVES ARENT CHANGING LENGTHS)
- the distance between the Z-lines decreases
- each I-band gets shorter
True or false: Thin and thick filaments get shorter/thicker when contraction occurs.
FALSE
The filaments DO NOT CHANGE LENGTH!! The sarcomere decreases in length because the filaments are SLIDING PAST EACH OTHER
**During skeletal muscle contraction, ________ and _______ filaments slide past each other in a repeating cycle
- myosin
- actin
**thick and thin?
How does muscle excitation work? (In review)
Muscle excitation begins as a CHEMICAL SIGNAL from a motor neuron that is converted to ELECTRICAL CHANGES at the sarcolemma
and back into a chemical signal (Ca2+) in the sarcoplasm
Excitation causes INCREASING CALCIUM LEVELS
An excited muscle begins to contract after CALCIUM LEVELS INCREASE and will continue to contract as long as calcium remains elevated
How does calcium affect troponin-tropomyosin interactions?
Calcium interacts with the troponin-tropomyosin complex of the thin filament, revealing the myosin-binding “active site” on actin
- when calcium interacts with the troponin-tropomyosin complex on the thin filament, it reveals an active site on actin
- this active site allows myosin to bind to actin
this active site is also referred to as the myosin site or myosin-binding site
Describe the structure of a thin filament:
- actin helix
- tropomyosin coil that wraps around the actin helix
- troponin complex found periodically on the actin helix
What is the best way to characterize the role of Ca2+ in muscle contraction?
Elevated Ca2+ allows contraction to occur by revealing actin’s binding site for myosin
True or False: Calcium has a direct role in contraction.
FALSE
Calcium has NO DIRECT ROLE in contraction - It permits contraction to happen by clearing the way so that myosin and actin can interact.
Calcium binds to TROPONIN and exposes actin’s binding site for myosin / reveals the myosin-binding site
MYOSIN IS WHAT BINDS TO ACTIN’S ACTIVE SITE
Stage 1 of Contraction: Calcium
Calcium has NO DIRECT ROLE in contraction - It permits contraction to happen by clearing the way so that myosin and actin can interact.
Calcium is released (from excitation)
Calcium binds to TROPONIN and exposes actin’s binding site for myosin / reveals the myosin-binding site
MYOSIN IS WHAT BINDS TO ACTIN’S ACTIVE SITE
Stage 2 of Contraction: Binding
Now that calcium has revealed the myosin-binding site on the thin filament/actin, the active sites are exposed
Cross-bridges form when myosin heads bind to actin
Stage 3 of Contraction: Power Stroke
This is called the POWER STROKE
Myosin head binding to the myosin-binding sites causes a reaction where the neck/hinge of the myosin monomer goes from extended to acute (STROKE)
The neck pivots and causes the filaments to slide past each other, creating sarcomeres (STROKE)
Once this occurs, the ADP+P energy that was bound to the myosin monomer are released (POWER)
Stage 4 of Contraction: ATP Binding
Another ATP comes in and the cross-bridge falls apart
Myosin head lifts off the actin’s myosin-binding site and another cross-bridge can form now that the previous one has detached
Stage 5 of Contraction: ATP Hydrolysis
ATP hydrolysis “recocks” the myosin head
(Basically restores the energy the myosin head needs to perform the cycle again)
ATP breaks down into ADP+P and the myosin is “recocked” and reactivated
What is troponin?
- molecule consisting of three globular subunits
- one subunit binds to tropomyosin, locking them together as a troponin-tropomyosin complex
- second subunit binds to one G-actin, holding the troponin-tropomyosin complex in place
- third subunit has a receptor that binds two calcium ions
- SITE FOR CALCIUM BINDING TO REVEAL MYOSIN-BINDING SITES
- Resting Sarcomere
In resting sarcomere, each myosin head is already “energized” charged with the energy that will be used to power a contraction
Each myosin head points away from the M line
In this position, the myosin head is “cocked” like a spring in a mousetrap
Cocking the myosin head requires energy, which is obtained by breaking down ATP into ADP+P
At the start of a contraction, the ADP+P remain bound to the myosin head
- Contraction Cycle Begins
Excitation occurs and a series of interrelated steps begin with the arrival of calcium ions within the zone of overlap in a sarcomere
- Active Sites Exposed
Calcium ions bind to troponin, weakening the bond between actin and the troponin-tropomyosin complex
The troponin molecule then changes positions
Rolls the tropomyosin molecule away from the active sites on actin
Allows interactions with the energized myosin heads
- Cross-Bridges Form
Once the active sites are exposed, the energized myosin heads bind to them, forming CROSS-BRIDGES
- Myosin Heads Pivot
After the cross-bridges form, the energy that was stored in the resting state is released (ADP + P) as the myosin heads pivot toward the M line
This action is called the POWER STROKE
When the power stroke occurs, the bound ADP+P are released
- Cross-Bridges Detach
Another ATP binds to the myosin head, causing the link between the myosin head and the active site on the actin molecule to BREAK
The active site is now exposed and able to form another cross-bridge (YIPPEE!)
- Myosin Reactivates
Myosin reactivates when the free myosin head splits ATP into ADP+P
The energy released is used to “recock” the myosin head
When does myosin change the orientation of its neck? When does ATP hydrolysis happen?
- During the power stroke, myosin’s head is pulled from extended to acute
- The myosin head is RESET by ATP hydrolysis
DONT FORGET!! ATP is hydrolyzed (used - turned to ADP+P) to RESET the myosin neck, NOT while pulling on actin during a power stroke
ATP hydrolysis is needed for resetting the neck NOT for the power stroke
Power stroke happens for free!!
Which stage of the contraction cycle will continue as long as calcium is present and ATP supplies last? (Out of the 5 from the slides)
A supply of fresh ATP is needed
Stage 4 - when the cross-bridge needs to detach, a fresh supply of ATP is required to break the link between the myosin head and actin’s active site
Stage 0 of Contraction: At Rest
In resting sarcomere, each myosin head is already “energized” charged with the energy that will be used to power a contraction
At the start of a contraction, the ADP+P remain bound to the myosin head
Which stage of the contraction cycle will continue as long as calcium is present and ATP supplies last? (Out of the 5 from the slides)
The filaments move relative to each other
Stage 2 - when the power stroke occurs, this causes the filaments to slide past each other/contract
Which stage of the contraction cycle will continue as long as calcium is present and ATP supplies last? (Out of the 5 from the slides)
ADP is formed from ATP
Stage 5 - the fresh ATP is needed to “recock” the myosin head with ADP+P
Which stage of the contraction cycle will continue as long as calcium is present and ATP supplies last? (Out of the 5 from the slides)
Calcium (in the cytosol) is required to complete this step
Stage 1 - calcium that is released from excitation binds to the troponin on actin, revealing the myosin-binding site that allows the myosin monomer to bind/power stroke
You cannot get contraction working without the initial __________
CALCIUM
**What happens if a cell runs out of ATP?
- Calcium would build up in the sarcoplasm, because ATP is needed to operate the (primary - active transport) ion pumps that return Ca2+ to the sarcoplasmic reticulum
- The contraction cycle would be directly affected because myosin heads would not be able to bind ATP
**In what state of the contraction cycle would the myofilaments and sarcomeres become stuck without ATP?
(Attached/Detached or Contracted/Relaxed)
Filaments would be ATTACHED - it requires a fresh ATP supply in order to break the link between the thin filament and the myosin monomer
- filaments are attached if ATP runs out, cross-bridges are in place if ATP runs out, and without ATP there is no detachment of the cross-bridge
Sarcomeres would be CONTRACTED - there is no ATP to lower the calcium levels during muscle relaxation -> cannot actively transport Ca2+ ions
- sarcomeres are contracted if ATP runs out, calcium gets stuck in the sarcoplasm because ATP is needed to actively transport Ca2+ ions, everything gets stuck
The interaction of sliding filaments causes the _____________ to shorten, creating tension in the ________________
- SARCOMERE
- TENDONS
Summarize excitation-contraction coupling
- neural control
- a skeletal muscle fiber contracts when stimulated by a motor neuron at the NMJ, stimulus arrives in the form of an action potential at the axon terminal - excitation
- action potential causes the release of ACh into the synaptic cleft, which leads to excitation, the generation of an action potential in the sarcolemma - calcium ion release
- muscle fiber action potential travels along the sarcolemma and into T tubules down to the triads - contraction cycle begins
- the contraction cycle begins when Ca2+ bind to troponin, exposing the active sites on the thin filaments - cross-bridge formation begins - and continues - as long as ATP is available - sarcomeres shorten
- as the thick and thin filaments interact, the sarcomeres shorten, pulling the ends of the muscle fiber closer together - muscle tension produced
- during the contraction, the entire skeletal muscle shortens and produces a pull or tension on the tendons at either end
What causes tension in tendons to be produced?
Tension can only be produced by myosin heads that overlap with(and thus can bind) actin
the total amount of “pull” a thick filament can make on a thin filament depends on how many of its myosin heads can grab onto actin
The tension a muscle fiber produces is related to sarcomere length - when sarcomeres are either stretched or compressed compared to optimal resting length, tension production declines
What happens when muscle length is too short?
If the muscles START with compressed sarcomeres:
(1.6) mu meters
- there is a decreased length and reduced tension because of the extensive overlap of thin/thick filaments
- a decrease in the resting sarcomere length reduces tension because stimulated sarcomeres cannot shorten very much before the thin filaments extend across the center of the sarcomere and collide with or overlap the thin filaments on the opposite side
(1.2)
- no tension can form when thick filaments meet Z lines and sarcomeres cannot shorten any further
- tension production falls to zero when the thick filaments are pressed against the Z lines and the sarcomere cannot shorten further
What is the optimal resting length/conditions to produce maximum muscle tension?
Between 1.6-2.6 mu meters
At optimal lengths, the greatest tension is produced to the maximum number of cross-bridges that can form
- sarcomeres produce tension most efficiently within an optimal range of lengths
- when resting sarcomere length is within this range, the maximum number of cross-bridges can form, producing the greatest tension
How does tension rely on Ca2+ levels?
Tension can only be produced when active sites are available
Calcium is what binds to troponin and allows for active sites to be revealed
Tension also depends on Ca2+ levels
0 Ca2+ NO TENSION - NO ACTIVE SITES
4 Ca2+ - 4X TENSION
6 Ca2+ - 6X TENSION
What is a muscle twitch?
The contractile/tension response of a muscle fibre in response to a single action potential (the stimulus)
- involuntary contraction of fibres that make up a muscle
What happens when the muscle length is too long?
If the muscles START with stretched-out sarcomeres:
(2.6)
- reduces size of the zones of overlap means that fewer cross-bridges can form, thus reducing tension
- an increase in sarcomere length reduces the tension produced by decreasing the size of the zone of overlap and the number of potential cross-bridge interactions
(3.6)
- zero zone of overlap reduces to zero tension because there is no interaction between thick and thin filaments
- when the zone of overlap is reduced to zero, thin and thick filaments cannot interact at all
- the muscle fiber cannot produce any active tension, and no contraction can occur
- such extreme stretching of a muscle fiber is normally prevented by titin filaments and by surrounding connective tissues
What are the three distinct phases of a single muscle twitch contraction?
- Latent period (muscle excitation)
- Contraction phase (Ca2+ build-up)
- maximum tension development occurs between contraction and relaxation - Relaxation phase (Ca2+ removal)
Frequency of Stimulation and Muscle Fiber Tension
- Treppe
Each time a skeletal muscle fiber is stimulated and immediately after the relaxation phase has ended, the subsequent contraction will develop a slightly higher maximum tension than did the previous contraction
The increase in peak tension will continue over the first 30-50 stimulations
Called a TREPPE because it rises like steps in a staircase
Most skeletal muscles do not demonstrate treppe, however treppe occurs in cardiac muscle tissue
Frequency of Stimulation and Muscle Fiber Tension
- Wave Summation
If a second stimulus arrives before the relaxation phase has ended, a second/more powerful contraction occurs
The addition of one twitch to another in this way is called WAVE SUMMATION
Frequency of Stimulation and Muscle Fiber Tension
- Incomplete tetanus
A muscle producing almost peak tension during rapid cycles of contraction and relaxation is said to be in INCOMPLETE TETANUS
What causes summation? What is summation?
Repeatedly stimulating a single muscle fibre can cause summation of tension due to residual Ca2+ build up
Summation occurs because more Ca2+ enters the cytosol before all the original Ca2+ is removed, revealing more active sites
How is possible for more Ca2+ to enter the cytosol before all the original Ca2+ is removed?
Because ion transport by pumps is slower than movement through ion channels (like the RyR)
What is tetanus?
When persistent tension is produced by a repeatedly stimulated muscle fibre or muscle
Frequency of Stimulation and Muscle Fiber Tension
- Complete tetanus
Complete tetanus occurs when a higher stimulation frequency eliminates the relaxation phase
Action potentials arrive so rapidly that the SR cannot reclaim calcium ions - high cytosolic levels of Ca2+ prolong the contraction, making it continuous
Which of the following types of stimulation would be most effective at generation maximum (tetanic) tension production?
A. A single, very intense stimulus
B. 10 moderate stimuli, occurring 20 ms apart
C. 20 moderate stimuli, occurring 40 ms apart
B. 10 moderate stimuli, occurring 20 ms apart
stimuli need to be close together for interactions for contractions (tetanic) to occur
- incomplete/complete tetanus = decreasing time for relaxation, so the stimuli needs to occur faster
**What would happen to contraction (shortening) in an activated muscle if some external force pulls on the joint/tendon in the opposite direction at the same time?
Different types of contraction occur based on the balance between a muscle’s load and the force it is producing
What are concentric (shortening) contractions?
- muscle tension EXCEEDS the load/external force and the muscle SHORTENS
- total length of the muscle shortens as tension is produced
- produces movement at the joints
- an external load (opposing
force) on a muscle will slow the
rate of contraction (shortening)
during activation - concentric contractions produce movements at the joints
EX: UPWARD PHASE OF A BICEP CURL - RAISING THE DUMBELL
What are isometric contractions?
- the muscles produce just enough tension to balance an external load
- no change in length of the muscle
- muscle contraction without motion, USED TO STABILIZE A JOINT
- the muscle as a whole does not change length, and the tension produced never exceeds the load
- When the degree of muscle activation (internal tension produced) exactly matches the external force, there is contraction (tension production) without shortening
EX: HOLDING THE DUMBELL IN A STATIC POSITION
What are eccentric contractions?
- the peak tension developed is
less than the load, and the muscle elongates because of the contraction of another muscle or the pull of gravity - occurs when the external load is higher than the internal tension produced
- Although the muscle is activated (produces internal tension), it gets longer, not shorter
- Eccentric contraction can be used like a ‘brake’, slowing down movement at a joint produced by external forces
EX: THE DOWWARD PHASE OF A BICEP CURL - LOWERING A DUMBELL
Describe the Sliding Filament Model
Describe the Contraction Cycle
Concentric Contraction:
External force ____ Internal tension
Muscles will __________
Example:
Concentric Contraction:
External force < Internal tension
Muscles will SHORTEN
Example: Lifting a dumbbell (curling)
Isometric Contraction:
External force _____ Internal tension
Muscles will ___________
Example:
Isometric Contraction:
External force = Internal tension
Muscles will NOT CHANGE LENGTHS
Example: Holding a plank
Eccentric Contraction:
External force ______ Internal tension
Muscles will ___________
Example:
Eccentric Contraction:
External force > Internal tension
Muscles will ELONGATE
Example: Lowering a dumbbell (curling)
What are myofibrils made of?
Myofibrils are made of sarcomeres that contain thin and thick filaments that slide past each other, shortening the muscle fiber
The biochemistry of _______ and __________ and their interactions allows for the contraction cycle which produces filament movement.
- actin
- myosin
What is the role of calcium in muscle contraction?
The contraction cycle is gated by the presence of calcium which removes an obstruction for actin/myosin interactions, and depends on ATP, which is required for crossbridge detachment and myosin neck ‘recocking’.
The amount of shortening occurring in an activated muscle depends on the balance
between ___________and ___________forces acting on that muscle.
List the three types of contractions
- internal
- external
Three types of contractions:
a) Isometric contraction
b) Concentric contraction
c) Eccentric contraction
