Term
| How is muscle fiber strength determined in white muscle? |
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Definition
a. Myofibril diameter
b. Excursion- Longer fibers (i.e. more myofibrils) can shorten greater lengths |
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Term
| Why is the sarcolema important in lateral transmission of force during contraction? |
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Definition
| Cell membrane is in direct contact with basal lamina, which serves as a scaffold |
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Term
| Explain the general structure of a muscle |
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Definition
Sarcomeres make myofibrils (surrounded by endomysium)
Myofibrils make fascicles (surrounded by perimysium)
Fascicles make a muscle tendon (surrounded by epimysium) |
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Term
| How do the globular heads of myosin II relate to the rate of cross-bridge cycling in skeletal muscle? |
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Definition
1) MHC partially determines speed of contraction by ATP hydrolysis, but the speed of the MHC ATPase is modulated by two associated MLCs.
2) Remember, there are many MHCs expressed at different points in development and in different cell types. |
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Term
| Explain how myosin-binding to actin filaments is suppressed in resting muscle |
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Definition
Remember, each actin monomer in the alpha-helical twist has a MHC-binding site.
At rest, this site is filled with tropomyosin, which is related to actin by the heterotrimeric protein troponin (TnT binds tropomysoin, TnI binds actin and TnC rests between TnT and TnI). |
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Term
| Explain the “Sliding Filament Theory” of contraction |
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Definition
a. Net movement of myosin head towards (+) end of actin
b. Attached (short-myosin head w/o ATP linked to actin)
c. Released (ATP-binds to back of head, reducing affinity of head for actin and actin moves)
d. Cocked (ATP is hydrolyzed, but ADP and Pi remain tightly bound to cocked protein)
e. Force-Generating (Myosin binds weakly to new site on actin, Pi is released, power stroke causes Myosin to bind tightly to its original site and release ADP).
f. Attached state resumed |
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Term
| Explain the organization of actin and myosin in a sarcomere |
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Definition
a. Myosin and actin overlap in the “dark” A band
b. Actin binds to Z lines within I-band
c. Myosin tails attach to M-line and heads poin to Z-discs.
d. When the muscle contracts, myosin filaments pull actin filaments toward the M-line, shortening the sarcomere. |
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Term
| When examining a striated muscle cell at the molecular level, you notice repeats of the PEVK sequence. What does the presence of this sequence suggest to you and what is the importance of the molecule that it represents? |
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Definition
a. PEVK repeats are found in the large Titin monomers in their I-band protion and is important for passive tension in muscle fibers.
b. Remember, Titin stretches from the Z-disc to the thick filament and maintains the arrangement of myosin filaments within sarcomere as well as protecting shape following contraction. |
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Term
| Muscle fibers require a great deal of focalized protein production for contraction. How is this specificity maintained in fibers with expanding diameters? |
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Definition
a. Nuclear Domains stimulate quiescent satellite cells!
b. Nuclear domains contain “sole source providers” for given functions (i.e. Ach receptors localized to particular regions). If fibers stretch, these domains signal satellite cells to divide and extend the domain (“stem cell” like). |
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Term
True: False
Muscle cells have very well developed ERs, but fewer ribosomes then some other cell types. |
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Definition
False!
they secrete very little protein, so ER is not well developed, but ribosomes are! |
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Term
| How do T-tubules relate to muscle relaxation? |
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Definition
T-tubules are extensions of the sarcolema that extend across the surface of muscle fibers and invaginate fibers at the A/I band junction.
They connect to 2 sarcoplasmic reticulum networks that contain calcium during period of relaxation. |
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Term
| Explain how Excitation contraction coupling is both voltage dependent and calcium dependent. |
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Definition
a. DHPR activation is voltage-dependent/ RYR activation is calcium dependent.
b. Depolarization of t-tubules is sensed by dihydropyridine receptors (DHPR), which connect to the SR.
c. Depolarization opens voltage sensitive portion of DHPR, which causes a conformational change and opens RYRs (voltage-dependent).
d. RYR opening causes calcium release from SR into sarcomeric space (Ca-dependent) |
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Term
| How does intracellular calcium release cause MHC-binding to actin, thereby initiating muscle contraction? |
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Definition
a. Calcium binds to TnC subunit of troponin
b. Troponin conformational change kicks tropomyosin off of MHC binding site on actin helices
c. MHC binds.
d. Calcium-activated ATPase in SR pumps calcium from intracellular space. |
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Term
A patient is extremely sensitive to halothan and succinylcholine (anesthetic and depolarizing NM-blocking agent).
What is wrong and how might you treat? |
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Definition
a. Malignant hyperthermia (HM)
b. Mutations in RyR causes over-release of calcium from SR causing muscle rigidity and a hypermetabolic state. Ultimately muscle damage and hyperthermia follow.
c. Treat with Dantrolene, which is a muscle relaxant that acts directly on RyR (80% mortality without treatment). |
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Term
1) Explain excitation-contraction coupling
2) How does botox de-couple this? |
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Definition
1) Presynaptic neurons synapse on motor units at motor end plates, releasing Ach to bind to Ach receptors in the muscle membrane, which causes depolarization of the sarcolema.
2) Prevents Ach release from presynaptic neurons, causing muscle relaxation. TTX also acts at the NMJ to prevent Ach release |
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Term
True:False
Clinically-releveant NMJ blockers work post-synaptically |
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Definition
True.
Remember, they can work to induce-paralysis, but they will NOT PREVENT PAIN (still need anesthetics and/or analgesics) |
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Term
| How do Non-depolarization and Depolarizing NMJ agents differ? Which is more commonly used? |
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Definition
Non-depolarizing (more widely used) block Ach-receptor interactions)
Depolarizing agents induce persistent depolarization and cause desensitization of the receptor |
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Term
1) How do organophsphates induce neurotoxic effects?
2) How are they treated? |
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Definition
1) SLUDGE at nicotinic junctions
(salivation, lacrimation, urination, defecation, GI upset, emesis)
2) Treat with Atropine to block Ach action and Pralidoxime to reactive AChE (soldiers are issues these to treat neurotoxin effects) |
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Term
| What are the 3 characteristic motor units? |
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Definition
Each unit is innervated by a number of alpha-motor neurons
1) Fast fatigable (FF) (longest motor neurons)
2) Fast fatigue resistant (FR)
3) Slow (s) with smallest motor neurons
Remember, short motor neurons are activated first. |
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Term
| Distinguish isometric and isotonic actions. Concentric and Eccentric actions? |
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Definition
1) Isometric is contraction without length change, while isotonic involves change in length with tension
2) Concentric is shortening muscle action and eccentric is lengthening of muscle (Muscles ONLY PULL). |
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Term
| How does the concept of “temporal summation” relate to muscular force generation? |
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Definition
Fast- Higher stimulation rates lead to greater force generation, because muscle fibers are always primed by available calcium.
Explanation
When muscle cells are stimulated at low frequencies, released calcium can be taken up before subsequent contractions and full relaxation is achieved (twitch).
If stimulation rates are slightly higher (10-20hz), some relaxation can occur b/w stimulations, but only (unfused tetany).
At high stimulation frequencies, fused tetany occurs, as calcum is released faster than it can be reclaimed, causing continuous cross-bridge cycling and higher force development. |
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Term
| Explain the length-tension relationship seen in isometric muscle contraction |
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Definition
IN VITRO
Product of actin/myosin overlap
1) At "plateu," force/length is constant (optimal actin/myosin overlap)
2) The "descending limb" of the graph occurs when sarcomere length is too long and there is poor overlap (excitation without contraction)
3) The "ascending limb" occurs when lengths <2.0 um are tested, where actin filaments are forced past the M-line and begin to overlap with actin filaments from the adjacent sarcomere, resulting in opposing force to contraction (at 1.7 um, myosin filaments intrude Z-discs and no further shortening occurs) |
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Term
| How does passive muscle tension arise (as seen in isometric contraction graph) at sarcomere lengths greater than the optimal? |
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Definition
Titin!
Acts as a spring and is responsible for the passive properties. |
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Term
Describe the biochemical basis of the force-velocity curve of isometric muscle contraction.
What is the clinical relevance of this? |
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Definition
1) At high contraction velocities, the cross bridge cycling approaches the maximum and fewer myosin/actin cross bridges will be engaged at any given point in time
2) At low velocities, myosin and actin can engage to a greater degree, allowing more force generation to move greater loads.
Muscle is gained at SLOW SPEEDS |
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Term
| Why is it important to help patients in physical rehabilitation build muscle slowly? |
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Definition
| At low velocities, myosin and actin can engage to a greater degree than at higher velocities, allowing more force generation to move greater loads. |
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Term
| What does the 3-D Length-tension velocity graph tell us? |
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Definition
1 At high velocities, sarcomere length is largely irrelevant and developed force will be low
2) At low velocities, sarcomere length is an important predictor for optimal force generation
3) At negative velocities, or "eccentric" actions, muscle velocity dominates sarcomere length in terms of force developed |
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Term
| What are the three standard types of fibers (metabolism-based) |
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Definition
1) Slow twitch oxidative (SO)
2) Fast twitch oxidative glycolytic (FOG)
3) Fast twitch glycolytic (FG)
Says nothing about protein composition as it relates to function |
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Term
| What are the 3 types of MHC found in human skeletal muscle and how do they function? |
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Definition
1) Type 1-
In slow twitch postural muscles such as the soleus
Rich in myoglobin and mitochondria.
Have the slowest contraction speed but they are fatigue resistant because of oxidative capacity.
2) Type 2A- Fatigue resistance and high-speed contraction, but with a higher metabolic cost than type 2X.
3) Type 2X- highest contraction speed, but fatigue very quickly making them almost useless. With exercise, they can express MHCIIA and develop increased oxidative capacity (they can also revert back). |
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Term
| Why are MHCIIA changed to MHCIIX in bed-rest patients? |
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Definition
| Saving energy w/e expenditure of oxidative energy. |
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