Exam 2 Flashcards
Name the four theories which explain muscle contraction.
sliding-filament theory, excitation-contraction coupling theory, steric-block theory, and cross-bridge theory
Define the sliding filament theory.
Thin and thick myofilaments are fixed in length, but move in relation to each other
What is the result of the sliding filament theory?
Change in sarcomere length and therefore muscle shortening
What zones/bands of the sarcomere are effected in the sliding filament theory?
H zone gets narrower
I band becomes shorter
Does the A band change with the sliding filament theory?
No, the myosin length are constant
Define the excitation-contraction coupling theory.
Process by which the muscle membrane AP leads to the release of intracellular Ca++ from SR, thereby causing muscle contraction
What is considered the second messenger?
Ca++
Give the three basic steps to excitation-contraction coupling.
1) AP propagate along motor neuron to motor end plate
2) ACh binding at motor end plate
3) New AP is initiated on the muscle fiber plasma membrane
What specialized membranes are important to the excitation-contraction coupling theory?
T-tubules and Sarcoplasmic Reticulum
What two functions do the specialized membranes serve during the excitation-contraction coupling?
1) Take the AP from surface down into center of the cell
2) Allow contractile proteins to interact
What is the T tubule system?
Invaginations of surface membrane which transmit excitation signal from along the surface membrane down deep into the muscle fiber.
What is the SR and what channels/receptors are important to the excitation-contraction coupling?
The SR stores and releases Ca++ and has a DHP receptor on the T side of the terminal cisternae and the RYR on the SR side.
What type of channel is the DHPR?
Voltage dependent L type Ca++ channel
What three proteins play a major role in Ca++ binding?
Calmodulin binds Ca++ in the cytosol, Calsequestrin binds Ca++ in the SR, and TnC binds Ca++ on the troponin complex.
Define the Steric Block Theory.
The blocking of binding sites within the thin filament proteins which is required for muscle action.
What are the three subunits of Troponin and what is their function?
TnC: Ca++ binding site
TnI: Helps position Tropomyosin on Actin
TnT: Loose attachment to Tropomyosin blocking binding site
What kind of change does Ca++ binding to TnC cause?
conformational change
Describe tropomyosin structure.
Tubular regulatory protein on actin which blocks myosin binding site
What is the result of Ca++ uptake?
Muscle relaxation
What drives the unbinding of Ca++ and TnC?
SR sequestering Ca++
How long does force generation continue for?
As long as neural impulses are arriving at the NMJ and Ca++ concentrations remain high in the myofilament region
What happens to Ca++ and force when the neural impulse stops?
Reduced Ca++ and reduced force
Define the cross-bridge theory.
Movement of the thin filament across the thick filament via myosin and actin binding
What area of the thick filament is the cross-bridge formed from?
The heavy meromyosin (HMM) of myosin heavy chain (MHC)
Where is the ATPase located on the thick filament?
The HMM
What is ATPase?
An enzyme which hydrolyzes ATP on the thick filament
What is LMM and where would it be located on the thick filament?
It is the light meromyosin and is located in the tail region.
What is S1 and S2 on the thick filament? Explain from the hinge point as reference
From the hinge up, first is S2 followed by S1 on the heads
How can the action of cross-bridge be described?
As a ratchet
How often does the ratcheting occur?
Repeats as many times along the length of the fiber creating an overall large amount of shortening in the muscle
At any given time, how many of the total cross-bridges are attached to Actin and producing force during contraction?
1/2
Describe the first step of the cross-bridge theory based off of the conclusion of the previous cycle
The ATP bound to myosin is hydrolyzed to ADP +Pi which energizes myosin.
If enough cytosolic Ca++ is present, TnC becomes bound and allows for what?
Myosin to bind to Actin, allowing for formation of the cross-bridge
Describe the second step of the cross-bridge theory based off the recent hydrolysis of ATP and attachment.
The stored energy is released resulting in movement of the cross-bridge
What is the movement of the cross-bridge referred to?
The power stroke
What must attach to myosin after the power-stroke is complete? What step is this?
ATP binding allows for the myosin to detach. This is the third step
Describe the fourth step of the cross-bridge theory based off of the recent ATP binding to myosin.
The ATP is hydrolyzed, with free energy being bound to myosin. This allows the myosin to be ready to repeat the cross-bridge cycle.
What general skeletal muscle responses are analyzed during this section?
The force-frequency relationship, length-tension relationship, force-velocity relationship and the force-pCa++ relationship
Describe isometric, concentric and eccentric contractions.
Isometric resembles a fixed length
Concentric is when the external force is < force developed by the muscle . Shortening.
Eccentric is when the external force is > force developed by the muscle. Lengthening.
Describe in-vivo
In the living organism
Describe in-situ
In position or in original place
Describe in-vitro
In glass
Which experimental set-up require the muscle to be stimulated electrically?
In-situ and In-vitro
What does external stimulation of a muscle fiber allow for?
Precise control of freq. of recruitment, muscle length and load characteristics.
What is a twitch contraction?
The smallest contractile response that can be elicited
What type of delay is present in twitch contractions? What is this from?
An electrochemical delay is present for conductance>T Tubules>SR>Ca++ release> etc…
What is the twitch utilized to determine?
The elementary contractile capabilities of muscle
What is a tetanic contraction?
When a second and subsequent stimulations occur before complete relaxation.
What is the additive effect from tetanic contractions called?
Summation
What is one reason that tetanic contractions are additive?
There is already TnC bound with Ca++
How long does contraction and relaxation take?
~100 ms
How long does Excitation (With Ca++ release) take?
~5 ms
What is temporal summation?
If after the 1st impulse, a 2nd impulse is delivered before 100 ms has elapsed, the muscle will be signaled to contract before fully relaxing
What is fusion in regards to temporal summation?
The impulses appear smooth due to higher frequency of pulses per second (Hz)
What is a state of unfused in regards to temporal summation?
The impulses appear jagged, with notable difference along the impulse line. Lower frequency
Describe an isometric muscle action and label: Active force, contraction time, peak rate of relaxation and half and late relaxation times.
A
What is the force-frequency relationship?
Demonstrates the influence of modulating frequency of recruitment on force output.
Does the force-frequency relationship represent one contraction or multiple different contractions?
Multiple contractions all at different settings of frequency of stimulation
What is the fusion frequency?
The lowest frequency for which oscillations in force are not evident
What is peak force on the force-freq. relationship?
highest force obtained
What is the twich:tetanic ratio?
The developed force of a twitch contraction compared to peak force w/ summation
What is the value of the twitch:tetanic ratio?
Able to identify differences in fiber types and conditions affecting muscle (ie: cancer cachexia)
What is the length-tension relationship?
The isometric force of a muscle maximally activated is dependent upon its length
What are the 3 parts of the length-tension curve?
1) Ascending limb
2) Plateau
3) Descending limb
What type of animal was used to determine the length-tension relationship?
Frog muscle
Which way should you view the length-tension relationship?
Left
T or F: The length-tension relationship is a plot of one muscle contraction.
False: It is a plot of individual lengths and their correlated force production
What are the lengths of myosin and actin, as well as the total?
Myosin: 1.65 micrometers
Actin: 2.0 micrometers
Total: 3.65 micrometers
What is the y axis on the length-tension curve?
What is the x axis on the length-tension curve?
y=Tension
x=Length
What happens after the length reaches 3.65 micrometers?
There is no overlap, therefore there is zero development of force due to no actin/myosin interaction
Summarize the descending limb of length-tension curve
As muscle shortens, overlap is possible. As it shortens, more overlap occurs.
There is an increase of force with decrease in length until ~2.2 micrometers
Summarize the plateau phase of the length-tension curve
Continues to shorten, but no increase in force.
Why does the plateau phase of the length-tension curve result in no increase in force?
The actin start to approach the bare region of the thick filament where there is no HMM, only the myosin backbone (LMM).
What is Po? What is Lo?
Po= The maximal tetanic tension generation (optimal) Lo= The optimal length for force production
These are correlated
Describe the ascending limb of the length-tension curve
As the length decreases, the force decreases
Why does the ascending limb of the length-tension curve result in less force?
At ~2.0 micrometers, actin filaments from one side of the M line start to juxtapose the actin filaments from the other side.
What happens when the sarcomere shortens <2.0 micrometers?
Actin overlap to the other side creating a double overlap which there is both a pull and a push on the filament. This negates further increase in force development.
What are the two portions to the ascending limb?
Shallow and steep
What is the range for the shallow section?
~2.0-1.87 micrometers
What is the range for the steep section?
<1.78 micrometers
What happens at the myosin filament when shortening goes below 1.78 micrometers?
The myosin begin to interfere with shortening as it abuts the Z-disk
What is the passive portion of the length-tension curve?
Represents tension generated if a muscle is stretched without stimulation
Where on the curve is passive tension almost zero?
~Lo
What happens to the passive tension as the muscle is stretched?
Increase passive tension
When in passive portion of the length-tension curve, what structural item is thought to be responsible?
Titin
T or F: Passive tension can play a role in the absence of muscle activation.
True
In regards to length-tension relationship, what happened in both 1985 and 1986?
1985: Origin of most passive tension being with the myofibrils
1986: The size of the protein responsible for passive tension is very large
How many amino acids are in Titin?
27,000
How much does Titin weigh?
3 million Dalton’s
T or F: The weight of the titin protein revealed the “spring” like characteristics.
False: The sequencing of the amino acids is what revealed the spring like characteristics.
Explain the force velocity curve shape and what the changes mean for each variable
With increased force, there is slower velocity. With increased velocity, there is lower force.
What is P0 on the Force-Velocity Curve?
The maximum isometric force(at zero velocity=isometric)
What is V0 on the Force-Velocity Curve?
The peak velocity at which 0 force is registered
When you extend the force-velocity curve to include lengthening of the muscle, what does it look like?
A
What is the ultimate reason that with increased velocity of shortening you are able to contract less force?
Skipping of binding sites for actin/myosin interaction due to the rate constants of attachment/detachment for normal cross-bridge interactions being too slow. Results in less force
What does the force-pCa++ relationship represent?
The lower the Ca++ concentration, the lower force production
How is pCa++ often represented on the curve?
The negative log of Ca++ concentration is used the X axis
T or F: Force increases indefinitely with increased Ca++ concentration
False, the curve reaches a point of plateau where Ca++ concentration no longer affects the force production
What experimental method is used to test the force-pCa__ relationship?
Skinned muscle fiber is immersed in solutions of varying Ca++ concentrations
How does the force-pCa++ relationship related to fatigue theory?
With increased lactate, there is an increase in Hydrogen protons which can interfere with Ca++ binding to TnC, therefore reducing the capability to produce force
How should you analyze the force-pCa++ relationship curve?
Pick a Ca++ concentration on the X axis and check the force correlated with it
Define a motor unit
An alpha motoneuron and all of the muscle fibers it innervates
Where is the motoneuron cell body located?
In the ventral root of the spinal cord
What is the axon?
The long projection extending from the cell body
Describe: Cell body to muscle fiber
1) Each cell body projects one axon through the ventral root
2) Axon extends to innervate a particular muscle
3) Axon branches many times and normally each small terminal branch innervates a single muscle fiber
How many motor units will a whole muscle have?
Many
How are motor unit axons distributed on the muscle belly?
They are spread out throughout the muscle to create a wider response throughout the muscle
T or F: A motor units fibers may be directly adjacent to another motor units fibers.
True, this creates a widespread response from the muscle with each motor unit adding to the response
How many fibers within a motor unit are stimulated and contract when an AP is propagated?
All fibers
Smaller muscles of the foot/hand have ___ motor units
Fewer
Larger muscles of the trunk area have ___ motor units
More
Muscles of the eye/face have a ___ number of ___ motor units
Large number of small motor units
T or F: The number of muscle fibers in a given motor unit varies.
True, based off of the need for motor control.
About how many muscle fibers would be in a motor unit for fine control?
relatively few(10s-100s)
About how many muscle fibers would be in a motor unit for gross control?
much more than fine, (1000s) because fine control isn’t needed
What three metabolic schemes can identify muscle fiber type properties?
Myofibrillar ATPase (MATPase), Succinate Dehydrogenase (SDH), and Alpha-Glycerophosphate Dehydrogenase (A-GC)
What three metabolic pathways are discussed?
Oxidative phosphorylation, Fatty acid oxidation, and Glycolysis
When typing a muscle fiber, what properties are considered?
Morphological, contractile and metabolic
What schemes provide the most benefit when typing a muscle fiber?
Those that can be related to other types of measurements
What are most modern schemes based around when typing muscle fibers?
Myosin molecules
What property links the fiber type to the function?
Metabolic
Explain histochemical methods of typing.
Enzymes in thin slices of skeletal muscle can be reacted to visualize enzyme activity
What does MATPase help identify?
Distinguish between fast and slow
What is MATPase directly proportional to? Why?
Sliding velocity. Myosin molecule activity limits the rate of muscle contraction
Briefly explain how MATPase is stained.
Inorganic phosphate is reacted w/ Ca++ to produce a white precipitate CaPO4 which is converted to CoS2
What does a darker MATPase stain represent?
Faster velocity due to fast fibers hydrolyze ATP quicker resulting in more inorganic phosphate when time is controlled
What does Succinate Dehydrogenase (SDH) distinguish?
The level of oxidation among fibers
What organelle is this test associated with?
Inner mitochondrial membrane (bound to cristae)
What is SDH and what is its job?
It is an enzyme that is responsible for oxidizing succinate to fumerate in the citric acid cycle
Describe the SDH reaction
Succinate + NAD+ -> Fumerate + NADH
What is added to the SDH histochemical method to distinguish visually?
Purple tetrazolium salt
What does a histochemical result of dark purple speckled appearance mean?
Oxidative
What does alpha glycerophosphate dehydrogenase distinguish?
The level of glycolytic potential among fibers
Is Alpha-GC speckled or continuous in stain?
It is continuous throughout the cell and not contained to a specific organelle
What can 95% of muscle fibers be classified as?
FG, FOG or SO
Briefly describe the immunohistochemical method.
Use antibodies for protein identification. This is the gold standard for determining fiber types
What is the main molecule looked for and how many are identified in humans and rats?
MHC
Humans: 1, 2A and 2B
Rats: 1, 2A, 2X and 2B
Briefly describe electrophoresis separation of MHC.
Pulverize muscle, centrifuge, SDS PAGE, Electrical stimulation to get negative proteins towards bottom, Protein plinko(smaller go farther down)
T or F: Humans have 3 genes for MHC and 4 expressed at protein level.
F: Humans express 3 at the protein level and 4 at the gene level
Look at charts for fiber typing and corresponding MHC
Do it!
Look at chart for protein differences among fiber types
Do it!
T or F: Hybrid fibers are more common than pure fibers.
T: there are many variations in fiber type allowing for a lot of fiber
Explain the distribution of fiber types when it comes to: ATPase, Tension Cost and Contraction Velocity
High to low
ATPase: 2B,X,A AND 1
Tension cost: 2B,X,A AND 1
Contraction Velocity: 2X,A/X,A, 1/2A AND 1
T or F: A faster fiber needs a better SR
True, due to the need to release and uptake Ca++
What are the 3 categories for motor unit classification? What are they based on?
FF: Fast Fatigable
FR: Fast Fatigue Resistance
S: Slow
Twitch tension, fatigue index and behavior of tetanic tension(Sag?)
What size nerve is correlated with fast fibers? What impact does this have on depolarization?
Fast fibers are associated with larger nerve sizes. This means that there is more surface to depolarize
What is the twitch tension for FF, FR, and S?
FF: high
FR: moderate
S: low
What is the contraction time for FF, FR, and S?
FF: fast
FR: fast
S: slow
What is the fatigue index for FF, FR, and S?
FF: Low
FR: Moderate
S: High
What is the Sag presence of FF, FR, and S?
FF: Yes
FR: Yes
S: No
What type of fiber is associated with FF, FR, and S?
FF: Fast glycolytic
FR: Fast oxidative glycolytic
S: slow oxidative
Describe the fatigue index.
Based upon the initial tension and so forth for two minutes
Highly fatiguable: <25%
Fatigue Intermediate: Between 25-75%
Fatigue Resistant: >75%
Describe the method for calculating fatigue index
A 40 Hz stimulus occurs for 1/3 sec w/ 2/3 sec rest, every second for two minutes measuring force degradation.
What two ways can the nervous system vary muscle force?
stimulation frequency and motor unit recruitment
The size of ___ is directly related to the recruitment? IE: Smaller is easier to recruit
motor unit
Recruitment patterns are ___, not sequential
additive
Explain the size principle
Recruitment of fibers matches the reason they are being recruited. Walking only requires type 1 fibers, while sprinting would require the type 1 fibers, with type 2 in addition for speed.
Fiber recruitment is usually determined by the amount of ___ or ___ necessary to perform that task.
force or power
What is rate coding?
The frequency of muscle fiber stimulation affects the force output. Increased freq.= Increased force
With recruitment of muscle fibers, forces are ___ to each other.
Additive
What is orderly recruitment?
Recruitment will occur in smaller/easier to depolarize fibers first (S or Type 1) followed by those that are larger (FR then FF)
What is the biochemical rationale for orderly recruitment?
Small motor units typically contain type 1 fibers and motor unit size progresses through the fiber types(1 to 2b)
What is the smooth increase in force rationale for orderly recruitment?
Increments in force will be small at low efforts and increase in proportion to absolute force expected
What is the orderly recruitment mechanism? Why?
Alpha motoneurons that are small are likely to correspond to the smallest motor unit size, this results in less energy used to recruit small motor units and increase recruitment if needed to preserve energy
When looking at a motor unit, smaller motor units will reach threshold with ___ current than large cells.
less
What is the order of motor unit recruitment?
S-FR-F INT-FF
How much will rate coding increase mean force by?
10 fold
How much will recruitment increase mean for by?
100 fold
There are two views on contributions to force production, what are they?
- At low forces, recruitment is more important followed by increased firing rates to increase output
- Recruitment is important at all force levels
What does recruitment vs. rate coding really depend on?
The location and/or function of the muscle
Small, distal muscles rely more on ___ for development of large forces
firing rate
Large, proximal muscles continue to ___ additional ___
recruit additional motor units
It has been observed that recruitment of additional motor units is associated with a transient drop in ___ of motor unites previously active. What does this provide?
Firing rate
smooth increase in force
What four ways may override the size principle?
- Recruitment order may be altered by sensory stimuli
- Motor unit rotation so that some are given a rest during prolonged contractions
- Lengthening contractions may have fast motor units be selectively recruited
- Rapidly executed movements may result in fast motor units being selectively activated
