Vet physiology lecture package #2
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What is the functional contractile unit of the muscle?
Thin filaments are? Thick filaments are?
What makes skeletal muscle have its outward striated appearance?
Its all orientated in one direction
A muscle fiber is a single cell and is called a
The myocyte is made up of
Myofibrils which allow for contraction
Describe where each is found on the sarcomere
- H zone = light area inbetween 2 darker areas, What is shrunk under contraction
- Z disk = is at the end of the sarcomere, there is one on each side and is a solid line
- A band = The darked band from myosin end to myosin end Includes in it the H zone
- I band = On 2 sides of the Z disk, ibetween 2 A bands, essentially on the edge of the sarcomere snugged up against the Z disk
(see picture on page 3 is best)
What is a myoblast?
Immature muscle cell
How many nucleuses in a muscle cell?
Where do we typically find nuclei on the muscle cell
On the outer edge
When the cell generates force the sarcomere
So according to the sliding filament theory do actin and myosin shorten at all during contraction?
No they actual actin and myosin don't shorten they just slide together and finger hold together type deal
If a sarcomere is overly stretched do we see the same ability to contract?
No it slowly loses ability to contract and once the actin and myosin are completely separated it no longer can contract cause they are not touching
Can a sarcomere contract indefinitely?
- No the amount of force a sarcomere cn give off during contraction has an optimum point, once actins start to overlap it does not get the same amount of force and quickly starts to lose strength
- Sarcomeres have a narrow range of optimum force generation
Main portion of myosin is what?
What decorates the mysosin tails?
2 Heads intertwined
What part of myosin actually binds to actin?
Where would you find the myosin heads on a filament
Sticking out the sides
What shape is actin?
Globular almost completely sphericaql
How does actin associate with itself?
In long intertwined chains like 2 strings of pearls
What are TnI, TnC, TnT
- TnI = Inhibitory troponin
- TnT = Tropomyosin troponin
- TnC = Calcium troponin
What do TnI, TnT, and TnC make up? What is its purpose?
- Troponin complex
- control tropomyosin
What is the purpose of tropomyosin?
Cover the binding sites on actin
Define a motor unit
A motor neuron and all the muscle fibers it innervates (functional contractile unit)
Define a motor nerve
A bundle of motor neurons (could even be different types) (innervates many motor units)
When a motor nerve is stimulated physiologically are all the motor units within it simultaneously stimulated?
No they can be different lengths and types so it doesn't work that way
What is often the neurotransmitter at a meuromuscular junction?
What is a neuromuscular junction?
Synapse between a neuron and muscle fibre
Receptors on the muscle fiber (post neuromuscular junction) are what kind of channels?
Ligand gated channels
Binding of acetylcholine to its receptor on a muscle fiber causes what?
- Na gates to open
- muscle cell depolarization and action potential along th muscle membrane
So acetylcholines receptor in all essence is a?
Need clarification on Ca in muscle contraction see page 70 and 71 of cunninghams physiology
What si the t-tubule
Transverse tubule or a membrane invagination that carries action potential into the interior of the muscle cell
How does the t-tubule activate the Sarcoplasmic reticulum to release Ca into the sarcolemma
Through the activation of voltage gated calcium channels on the T-tubule the physical mechanical connection between the voltage gated and calcium gated channels channels allows for direct opening of the calcium gated calcium channel and calcium is allowed to flow intot he sarcoplasm from the SR
What happens when Ca leaves the SR
it diffuses into the sarcoplasm and batheses the sarcomere
How does the SR get calcium in the first place?
It is actively pumped into the SR from the sarcoplasm, this leaves too little Ca in the sarcoplasm to cuse contraction so that contraction only occurs upon stimulation
What is the name of the voltage gated Ca receptor
DHPR or dihydropyridine receptor
What is the name of the Calcium gated Ca receptor
Are Ryanodine and DHPR receptors actually connected?
Yes physical mechanically together
Is DHPR a regular calcium channel in skeletal muscles?
No not really more like a key for the SR
What are the 2 ways to open a ryanodine receptor?
- DHPR and T tubule depolarization
- Activation by Ca in Sarcolemma
Where is all the T tubule and SR interaction happening inside or outside cell
Remember this is all within the cell upon the myofibril
So T tubules travel where abouts on the sarcomere? So why is this relevant to Ca release and contraction?
- Along the Z line at the ends of the sarcomere
- Because that is not really where we need the calcium we need it closer to the actin or closer to the A band of the sarcomere which is more central to the sarcomere, because of thiswe need calcium to be released there more
Describe the process of getting more calcium to the middle of the sarcomere from the edges of the sarcomere
When the first calcium is released due to DHPR and Ryanodine interaction this Ca diffuses in the Sarcoplasm down along the myofibril opening up more and more SR Ryanodine receptors as we get more central to the sarcomere, this allows more calcium release near the active zone of the sarcomere.
Remember this is possible because of the ability of Ryanodine receptors to be stimulated by both DHPR and Ca
Where do we find more Ryanodine receptors in the SR near the end of the sarcomere by the T tubules or more central near the actin and myosin
- Central near actin and myosin where it is actually needed for contraction
- The Ca released near the T tubules is more just for kickstarting the rest
What do TnT, TnC, and TnI do?
- TnT = attaches to tropomyosin
- TnC = binds Ca
- TnI = Regulates actin myosin interactions
Acetylcholine receptors on the postsynaptic neuron are what kind of gate?
What is often reffered to as the feet of the the T tubule sarcomplasmic reituclum complex?
The ryanodine receptors
DHPR is what kind of channel?
VOltage gated Ca channel
Are myofibrils and sarcoplasmic reticulum inside the cell?
What is the T tubule essentially made of?
invaginated cell membrane
What is often reffered to as the "triad" structure?
Structure of sarco reticulum, t tubule and sarco reticulum
Which receptors would you expect to see farther in on the Z line not close to the T tubule?
Ryanodine receptors most likely
Why would we need more RyR receptors towards the middle of the Z line
Where actin and myosin overlap and need Ca to help them bind
WHen calcium is out fromnt he sarcoplasmic reticulum it is essentially where?
In the cytosol
Which part of the actual SR comes into contact with the T tubules?
The terminal cisternae
So once calcium is dumped out and the myofibrils contract how do they get to relax with all this calcium everywhere?
There is an active calcium pump called SERCA that uss ATP tp sequester Ca back into SR and allow muscles to relax
Does the peak of the calcium influx coincide with the peak in a twitch force?
No they are lagged off by a bit
So when one myosin head lets go to reset and move up for more contraction why does the actin not slide down like it does during relaxation?
Cause there are 1000's of myosin heads attaching to this actin ata a time
at our theoretical step one in the myosin actin binding cycle we have myosin unattached to action and a partially phosphorylated ATP on the myosin head. We have just had calcium come in and move tropomyosin now explain what happens all the way back to step one.
- Because of the partially phosphorylated ATP myosin is in its high affinity for actin state. Now that tropomyosin is out of the way it binds up and onto the actin binding sight.
- 2. When actin and myosin bind together actin acts a cofactor to assist in the phosphorylation of ATP and it breaks down thus causing the power stroke step and force generation. ADP and P are now released THIS RELEASE IS WHAT CAUSES POWER STROKE NOT THE ACTUAL BREAKING DOWN.
- 3. Now actin and myosin are stuck together until ATP comes and binds the myosin head, because it is unphosphorylated completely it is in a low affinity state and myosin seperates from actin.
- 4. Now that myosin gets a chance it partially hydrolyses the ATP to ADP and P stretched, this sets the head back into ready position and increase the affinity for actin again, we can now start back at one as long as there is still calcium or the next time there is calcium.
At what point will the actin myosin contraction cycle stop if there is no calcium?
It will not go past theoretical stage one where the actin and myosin are in high affinity for eachother by not attached
Describe rigor mortis in terms of our actin myosin binding and contracting cycle?
Rigor mortis would occur at stage 3 of our theoretical cycle, when myosin is bound to actin and waiting for an ATp to come release it from this bond. In death ATP production stops and therefore no ATP comes to get myosin off, therefore leaving the body in a tense semicontracted no moveable state
As soon as all myosin heads let go of actin what happens?
Actin filament slides back down
Is myosin able to hydrolyse an ATP by its self?
No it needs actin as a cofactor
How does tropomyosin block the myosin binding?
It physically gets in the way by blocking the binding site
Explain 2 places where calcium is used in a muscle contraction?
- In the pre neuromuscular junction to help exocytosis of the presynaptic vesicles
- Released from the SR into the intracellular plasma to stimulate myofibril contraction
Describe isometric contraction and isotonic contraction. Describe a situation where you would see each of them
- Isometric means the length or metric of the muscle do not change but it contracts, this implies a great increase in tension
- Isotonic contraction is when there is a change in leangth and therefore no great change in tension
- Iosmetric can be seen when lifting something too heavy to lift
- Isotonic could be seen when moving your arm
Why do we see a little blip of tension at first with isotonic contraction
while most energy goes into shortening the muscle there is a blip because the elastic elements of the muscle and tendon need to be stretched out so there is a little bit of tension at first
myosin ATPase activity is stimulated by?
Binding to actin
Force generation step of contraction results from ATP hydrolysis or ADP and P release?
ADP and P release
An isometric contraction has what type of velocity? How does weight effect the velocity of a contraction? The fastest contraction of a muscle will occur with what kind of load?
- More weight = slower contraction
- No load
What is the equation for power? For force to be generated what is needed? Therefore how much force is generated when there is no load? when is the optimum power occurring?
- P = F*V
- power = force times velocity
- resistance or weight
- Power is greatest at moderate force and velocity
Power is a synonym for
Work in other words
Does max velocity and max power coincide?
NO max velocity occurs when load is 0 and max power occurs when force is moderate
- Essentially temporal summation in muscles, same stimulation just occurring close together enough to create an additive response
- additional stimuli arrive after a twitch but before full relaxtion has occurred or elastic elements not completely recoild
What causes facilitation in muscles? Its not that the action potentials are building up...
The fact that the elastic elements are not needing to be stretched as much, when theyget stimulated they take longer than muscle cells to go back to resting and therefore this stretch in eleastic materials continually can allow more energy the next stimulation to go to tension or contraction and not to stretching
Describe recruitment in muscle cells. Compare it with facilitation.
- Essentially spatial summation, increasing tension due to increasing number of motor units
- Facilitation increase tension through the loosening of elastic tissues and allowing more energy to go to the tension
Why do we see an increased for during tetany to the same calcium levels?
Because they are being contantly stimulated not relaxed and therefore the eleastic elements are definitely not contracting and all force is going towards tension soon
Why does Ca have a pretty specific max in terms of stimulating the myofibrils to contract
Because if Ca gets too high than it can cause toxicities, this is why the muscle has other ways to increase force rather than increasing calcium, such as recruitment and facilitation
What is meant by incomplete tetanus?
When a muscle tension never reaches 0 but the stimulations are far enough apart that you can see a small droop in tension essentially allowing you to see individual twitches thus making it incomplete
Leading up to a tetanus in the force generation stage is an example of?
Describe what a muscle threshold is?
Amount of stimulus needed to elicit a twitch
- Muscle response to repeated stimuli with sustained force
- Individual twitches no longer evident
What is a refractory period?
Time after a twitch when a muscle cannot respond to a second stimuli
Why does it make sense that muscles can get energy from multiple sources?
If they didn't then they would be quite vulnerable to losing energy and being stuck
What are 3 pools of energy for muscles?
- Creatine phosphate - burst of energy short duration
- Oxidative ATP - slower production, more ATP per glucose
- Anaerobic ATP generation - no O2 needed, lactate production can cause acidosis
How does the muscle decide on what it will use for energy?
By what is most appropriate for the job
Describe how creatine phosphate creates energy?
Donating phosphate to ADP...
Assuming low O2 availability or energy demands higher than oxidative metabolism can supply, we see what energy product used up first? Then? which produces? And puts muscles into what kind of debt? Describe this phenomena.
- Creatine phosphate
- anaerobic muscle metabolism
- lactic acid
- oxygen debt
- Oxygen debt is the amount of oxygen neded to aerobically convert lactic acid produced into energy
So a slower rate of energy expenditure means that what can cover the energy costs mostly? meaning there will be less what? meaning a shorter?
Does oxidative metabolism take time to start up or does it just ramp up instantly?
- Through oxidative metabolism and not need to use other sources
- oxygen debt
- recovery period
- takes time to start up, this is usually where some oxygen debt is incurred regardless of rate of energy expenditure
Does oxygen debt accumulation depend more on length of energy expenditure or rate? Why?
- Because oxidative energy metabolism can produce energy over time and cover the costs of less intense work but when ther eis a high rate oxidative metabolism cant cover ti over a short or a long time
What do we see change in improved endurance for trained athletes?
- Increased oxidative capacity
- Some increased tolerance to lactic acid
- ability to ignore feelings of fatigue
The soleus is a? while the lateral rectus is a? What makes these differences in muscles? velocity of muscle contraction is determined them by?
- Slow twitch muscle
- fast twitch muscle
- basically have different types of ATPase in the myosin
- intrinsic myosin ATPase activity in different muscles
Type 1 red muscles are typically? Type 2B muscles are typically? Type 2A are typically? And are found where?
- slow endurance
- fast twitch
- fast oxidative super muscles
- only in non primates
Between type 1 and type 2B muscle fibers which would you expect to see more oxidative capacity in? What about glycolytic capacity? Which do you think has the larger diameter?
Which muscle type 1 or type 2B is the fastest? Which as the fastest nerve stimulation? Which is more fatigable? Which has the more excitable nerve? Why does this kind of make sense?
- Because we want the muscle that wont put us into debt being activated first cause if it can do most of the work we never need to go into debt
So are muscle fibers attached to a specific type and characteristic of motor unit?
In muscle with mixed motor unit types which muscle is activated first? when is the second activated?
- Slow twitch
- When more force is needed.
During a sustained contraction of a mixed fiber muscle what holds up the tension in the muscle the fast or slow twitch? What happens to the other? What happens to the force exerted by the whole muscle?
Does slow twitch ever lose significant force?
- slow twitch
- drops off to almost no tension generated
- drops off but stays at some middle point because slow twitch keeps it going
What composition of muscle fibers do we see in quarter horses, thoroughbreds, and Arabians? What about heavy hunters and Shetland ponies?
what kind of trend do we see for type 2B fibers in horses?
- large amounts of type type 2A (high oxidative fibers)
- lower fast twitch a lot more slow twitch fibers
- Strange non systematic trends, not a lot of focus on this, me thinks this is not as good as the other fibers and so probably fills in the gap.
For the types of training please indicate what part fo the body is being trained and what is happening?
- Learning/coordination -INcreased rate and accuracy due to CNS training
- Endurance - increased oxidative capacity of all involved motor units, limited cell hypertrophy
- Strength - hypertrophy and enhanced glycolytic capacity of employed motor units
Hypertrohpy is the what?
Largening of muscle cells, essentially recruitment of myofibrils into the cells, NOT MORE CELLS BEING GAINED
When a muscle adds sarcomeres in length does this increase force? what about sid eby side
- No it increases velocity
- yes this is force
What is hyperplasia?
- Increase in muscle cells
- Very unusual from training
When a muscle adds sarcomeres in length does it change its "shortening capacity"? what is meant by this? What about when you add sarcomeres in parallel?
- Yes it does!
- Means the muscle has the ability to go through more change in length and shorten to a greater extent
- NO doesn not change shortening ability
See page 14 great summary
What happens to number of motor units and fibres/motor unit as an animal ages?
They get less motor units and more fibres per unit because the amount fo fibres doe snot decrease, it is kind of like the trend in hog production, less producers more hogs per farm
Is smooth muscle as disorganized as previously thought?
What is the dense body in a smooth muscle?
The equivalent of a Z disk in a skeletal muscle
Do smooth muscles still operate on the sliding filament theory? Does the way they go about this differ or is it the same?
Still sliding filament theory but differwent process
Actin or myosin attaches to dense bodies in smooth muscle?
Actin attaches to dense bodies myosin is suspended inbetween
What kind of pattern does dens ebodies and the actin myosin connection make in amsooth muscle?
A hair net pattern
What shape is a smooth muscle cell?
When a smooth muscle contracts which directions does it generate force in?
Essentially all directions cause it has "smooth sarcomeres" pointed in generally every direction to some extent so does not just contract lengthwise but sideways as well
Are smooth muscles organised in the same orientation for all the organs they cover?
- No they differ greatly (longitudinal and circular muscles for intestines, circular for arterioles, scattered for lining of ducts)
- In fact the way they contract these differs greatly as well
Does smooth muscles have T tubules? Do they have something functionally similar? What is it? What does it look like? Does it have actin and myosin?
- bubbles!, essentially area where sarcolemma is invaginated near the SR similar idea to T tubule
Differentiate between phasic and tonic contraction
- Phasic = a brief contraction along with a brief twitch
- Tonic = maintenance of force for extended period of time
what are some of the phases of a tonic contraction
- Phasic portion
- Maintenance portion
- Relaxtion portion
What type of contraction would a sphincter do?
Does tonic contraction always require energy?
No it can maintain its hold without energy, otherwise to keep sphincters closed and to contrict arteries would take half your energy
The maintanence phase of a tonic contraction can also be reffered to as the what phase?
Latch phase since there is latching between actin and myosin
We see phasic and tonic contraction in what kind of muscle?
During a tonic contraction the force exerted stays constant but what happens to the calcium and crossbridge phosphorylation?
THey drop down to almost basal or basal levels
Differentiate between phasic and phasically active smooth muscles
- Phasic is your standard relaxed muscle that has a phasic contraction and goes back to relaxation until needed again exaples could be the bladder or esophagus.
- Phasically active or cyclically phasic is when it runs on a spontaneous cycle such as in the stomache and intestine, keeping a wave going of phasic contraction and relaxation
Do tonic muscles need calcium like phasic ones do?
Not 100%, truly tonic muscle will need calcium to reach tonicity however then they will not need calcium until they relax and need to re tone, phasic muscles need calcium every time they contract
Differentiate and give examples of two different styles of tonic contraction.
- There is a partial tonic contraction which is seen in blood vessels and airways which never truly relaxes and goes in cycles of more contraction or less contraction
- Then there is a truly tonic muscle such as the sphincter which is fully contracted most of the time and onlyrelaxes for certain events
Is there troponin and tropomyosin in smooth muscle?
Instead of troponin and tropomyosin in smooth muscle what is there to control binding?
Accessory proteins on themyosin head
Smooth muscle is predominantly what regulated?
Thick filament regulated
what is the name of the hypothesis that allows the smooth muscle to stay contracted without using ATP
Latch bridge hypothesis
Is thin filament used in regulation of smooth muscle contraction at all?
Yes for fine tuning
What is the difference between a single unit muscle and multi unit muscle? We would expect multi unit to be activated _____ly? abd single unit to be activated _____ly?
Single is connected with gap junstions and act as one, multi unit act alone such as in the arteries, the smooth muscle in an area contracts, doesn't mean rest of arteries contract. However smooth muscle in gut is single unit cause 1 contraction causes more contraction down the line, helps squeeze
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