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What causes muscles to grow?
during hypertrophy, the fibers get bigger (length or diameter)
Where are motor neurons always located?
the cell body is located in the ventral gray matter of the spinal cord.
Where do motor neurons synapse in the muscle fiber?
They synapse in the center of the muscle fiber.
What direction does the action potential travel in a muscle fiber?
from the center to the ends
What is a distinct characteristic about skeletal muscle?
It is striated
What can be found inside a muscle fiber?
myofibrils, DNA, and mitochondria
What surrounds myofibrils?
only a protein sheath, no membrane
What makes up a protein sheath?
collagen and elastin
What happens to the muscle when the number of myofibrils increases?
the muscles get bigger
What is a sarcomere in a myofibril?
It spans from Z-line to Z-line, and is 22u
What is a Z-line?
it is a 3-D plate that supports actin and separates sarcomeres
What is a Z-line made of?
collagen and elastin
Why does actin have a depression in it?
For the myosin head to bind
Where is the M-line?
It goes through the middle of the sarcomere and separates each side of actin and myosin
Where is the A-band?
It extends from each head of the corresponding myosin heads
Where is the I-band located?
it is the region of only actin and no myosin, it contains the Z-line
Where is the H-zone?
contains only the myosin tails and the M-line, is the space between actin.
What happens to the H-zone during a contraction?
It disappears
Where is titin?
it spans from Z-line to M-line
How does actin appear?
thin and white
How does myosin appear?
thick and dark
What does troponin do?
It sits between actin
Where is tropomyosin?
covers the myosin binding sites
What gives the striped appearance of skeletal muscle?
the repeating A (dark) and I bands (white)
What is one way to increase the length of myofibrils?
Increase the number of sarcomeres
What are myosin heads preloaded with?
ATP
What is the first step in myofibril contraction?
calcium from the sarcoplasmic reticulum enters myofibril
After calcium enters the myofibril, what is the next step in contraction?
calcium binds to troponin
After calcium binds to troponin in the myofibril, what happens?
troponin undergoes the ligand effect
Once troponin has undergone the ligand affect due to calcium binding, what happens in myofibril contraction?
the ligand effect causes tropomyosin to move and unblock binding sites.
Once the binding sites are unblocked in myofibril contraction, what is the next step?
the myosin head binds to actin
After the myosin head binds, what is the final step in myofibril contraction?
heads rotate causing contraction
What is the first step in the release of myofibril contraction?
calcium that is pumped out of the cell goes back into the SPR, which stops calcium release
After calcium release from the SPR stops in myofibril relaxation, what happens?
no more calcium comes into the myofibril
What happens once calcium stops entering the myofibril, in myofibril relaxation?
calcium leaves troponin
Once calcium leaves troponin, what is the next step in myofibril relaxation?
troponin shape returns to the original shape
After the troponin shape goes back to normal, what is the next step in myofibril relaxation?
tropomyosin re-covers myosin binding sites
Once the myosin binding sites get recovered, what happens next in myofibril relaxation?
myosin heads release and quit rotating
Finally, once myosin heads stop rotating and release, what happens in myofibril relaxation?
the contractions stop.
Where is the SPR located in the myofibrils?
It surrounds myofibrils, like mesh
What are transverse tubules (T-tubules)?
They are parts of the membrane that get pulled into the cell and create pockets that myofibrils go through
Why do skeletal muscle cells and myofibrils need t-tubules?
Because the cells are so big that when sodium enters, it is too far away to change the charge in the center of the cell, so T-tubules bring the ECF towards the center of the cell
What is located on the membrane of the SPR that is important for calcium to exit?
Ryanodine Channel
What does a ryanodine channel do and what is associated with it?
It is a calcium specific 4-pillar channel, and it has a foot process right next to it
What happens to the ryanodine channel when muscle is relaxed?
it is closed
How big is a muscle fiber cell compared to other cells?
100x bigger
What is DHP and where is it located?
Dihydropyridine is a hand process on the T-tubule, and it interacts with ryanodine to ultimately open it and allow calcium efflux from the SPR.
How does the action potential that activates DHP occur?
Na in the ECF in the T-tubule goes into the ICF which increases the charge, causing K to exit via leak channels into the T-Tubule ECF.
What happens to DHP when an action potential occurs?
DHP takes on a new shape which then causes the ryanodine to change shape which then opens the calcium channels on the SPR allowing it to go into the myofibril and cause a contraction
How do ryanodine and DHP interact?
The hand process on DHP touches the foot process on the ryanodine channel, after DHP takes on a new shape
What causes rigor mortis?
After death, SPR releases calcium which is then exposed to the actin head. The pre-loaded myosin head binds causing a contraction, but there is no ATP release which keeps the muscles stiff
What is the latent period?
the time it takes before there is enough tension/ force to move the load
How long does a contraction last in skeletal muscle cells?
100 milliseconds
Can multiple action potentials fire during a previous contraction?
yes
What is the first step in the relaxation of muscle?
the motor neuron stops firing, also stopping acetylcholine release
After Ach release stops during muscle relaxation, what happens?
Ach is removed by Ach esterase
Once Ach esterase removes Ach what happens in muscle relaxtion?
the nicotinic channels close
After the nicotinic channels close following Ach removal, what happens?
AP stops in the T-tubules
Once the action potential has stopped in the t-tubules, what happens next in regard to muscle relaxation?
DHP receptor folds back to the inactive shape
When DHP goes back to its original shape, what happens?
ryanodine goes back to its inactive shape, and calcium channels close.
After ryanodine goes back to its original shape and calcium channels close, what happens? (muscle relaxation)
calcium stops being released from the SPR
Once calcium release from SPR stops, what happens? (muscle relaxation)
calcium ATPase puts calcium back into the SPR
After calcium is put back into the SPR, what happens? (muscle relaxation)
troponin and tropomyosin go back to the inactive position
Once troponin and tropomyosin are back in the inactive position what happens? (muscle relaxation)?
myosin heads and actin release
What can stop neuromuscular junction?
Drugs that bind to nicotinic receptors, preventing channels from opening, thus stopping Na influx and AP
What are the three drugs that can disrupt neuromuscular junction?
Curare
Sarin
Botulism Toxin
What does curare do that disrupts neuromuscular junction?
It acts as an Ach antagonist by binding to nicotinic receptors and closing them
What type of paralysis does curare inflict?
flaccid paralysis
What can curare be used for and what must be done if it’s used?
it can be used as an immobilizing drug during surgery but requires the doctor to breath for the patient.
What does Sarin do to disrupt neuromuscular junction?
it binds to Ach esterase causing it to become inactive, and forcing Ach to remain connected to the nicotinic receptor.
What type of paralysis does sarin cause and why
Flaccid paralysis; since the membrane potential stays above -70mV and the V.G. Na channels are inactive, it can’t get back to resting potential
How does botulism disrupt neuromuscular junction?
it attacks SNARE proteins in the axon terminal, which stops the fusion phase and decreases Ach release
What type of paralysis does Botulism toxin induce?
flaccid paralysis
What can botulism toxin (Botox) be used for?
Can be used in parkinson’s to slow down contractions
Contractile elements (CE)
myosin pulls on actin which then creates force (tension) that then pulls on connective tissue and applies force to the load (what you are trying to move)
Contractile Element Example
Arm
Series Elastic Component (SEC)
connective tissue and acts like a spring
Where are the Series Elastic Components?
in the z-lines, sheath around myofibrils, titin proteins, and connective tissues found in tendons and connecting muscle fibers
What is an isometric contraction?
when there is not enough tension to move the load
What is an isotonic contraction?
when the load is moved, so SEC equals the load
During an isometric contraction, what is happening to the CE, SEC, and the tension/force on the load?
The contractile element is at max force, the series elastic component is stretched, and there is an increased tension/force on the load.
What is unfused tetanus?
When an action potential fires before the contraction is finished, extending the time of the contraction
What is fused tetanus?
AP fire consecutively and the force/tension is increased significantly before plateauing.
What two things can cause tetanus to occur?
continued stretch of SEC (increases tension)
ryanodine channels remain open and continue to release calcium
Why are contractions longer than action potentials?
Because it takes longer for calcium to go in and out
What is the resting/optimum sarcomere length in regular muscle cells?
22u
At what length is the tension zero for muscle sarcomeres?
14u and 30u because there is no more room for overlap of actin and myosin, or they are no longer able to overlap
Why does congestive heart failure happen?
the sarcomere length is too long
In noncardiac cells, at what sarcomere length is the max tension/force?
22u
What is the resting cardiac length in cardiac muscle cells?
18u
What is the optimum sarcomere length in cardiac muscle?
22u
Why are the optimum and resting sarcomere lengths different in cardiac muscle?
because when the muscle is at 22u the heart pushes blood out with more force.
What are the sources for ATP?
Stored ATP (very small amount)
Stored as creatine
Glucose goes through glycolysis to make pyruvate and 4 ATP
2 pyruvates (from fatty acids) go through the krebs cycle to the mitochondria and make 34 ATP
What happens when there is not enough oxygen for the Krebs cycle?
Pyruvic acid is converted to lactic acid
Why does lactic acid make it difficult for actin and myosin to function?
Lactic acid gives off a proton, which creates a lower pH and causes the proteins to change shape
Prolonged concentrations of lactic acid can be a sign of what?
septic shock
During fatigued caused by the rapid firing of action potentials, what happens to the potassium concentration?
the concentration is elevated in the lumen changing the membrane potential and the Ek, making them more positive than -70mv. This means that the sodium channels can’t return to normal
How does lactic acid contribute to fatigue of muscle?
it increases the number of protons which lowers the pH and effects myosin and other proteins
How does oxidative metabolism contribute to fatigue of skeletal muscle?
it produces free radicals of oxygen, aka peroxide
How does prolonged release of calcium contribute to muscle fatigue?
Troponin’s calcium affinity decreases causing it to become less sensitive the longer calcium is there