Muscle 1 Flashcards
- Explain the structural basis of skeletal muscle contraction by constructing a sarcomere.
Sarcomere:
-Basic unit of contraction.
-Extend from one Z line to the next.
-Muscle cell = myofiber which has myofibrils made of myofilaments = actin and myosin.
(And regulatory proteins tropomyosin and troponin.)
- Describe the molecular structure of the sarcomere and the arrangement of contractile and linker proteins, and how this structural organization relates to contraction.
Actin:
- thin filament (in F-actin form) –> double stranded and helical in pearls on a string.
- Tropomyosin binds the actin (masks the binding site) and troponin binds tropomyosin.
- Thick filaments made of myosin –> composed of 3 pairs of proteins
- (1 pair of large/heavy chains and 2 pairs of small/light chains).
- Also form a helical chain with a globular head.
- Myosin head binds actin to cause shortening, and has ATPase activity.
- When relaxed, myosin can’t bind actin because tropomyosin covers binding site.
- After an AP, Ca rises, binds troponin = conformational change. Tropomyosin then exposes binding site so myosin can bind.
- Myosin pulls on actin and is stuck until it binds ATP –> , which allows it to dissociate –> hydrolysis of ATP ‘re-cocks’ myosin so it’s in a high-energy state and can bind actin.
- Get large scale movement because lots of sarcomeres can summate their effect, and many myosin-actin cycles occur in 1 contraction.
- Smooth muscle has no troponin, but still needs Ca.
- Ca binds calmodulin and this complex binds CaM kinase –> light chain gets phosphorylated –>then myosin can bind actin and generate force.
- This is much slower.
-Ca removed by Na-Ca exchangers and Ca ATPase pumps (or inactivation of the kinase and dephosphorylation).
- Define a myofilament and a myofibril and describe the relationship between myofibrils and the sarcoplasmic reticulum.
- Myofilaments = actin and myosin.
- Myofilaments –> myofibrils.
- Myofibrils each have their own network of SR.
- Myofibrils –> myofiber (muscle cell).
- Describe how connections of muscle contractile proteins are made to surrounding connective tissues and how they contribute to contractile force/movement.
Sarcolemma:
-muscle cell plasma membrane.
Epi-, peri-, and endomysium are connective tissues that connect the muscle regions.
-Epimysium = tough covering over entire muscle (belly).
-Perimysium = connective tissue around each fascicle.
-Endomysium = connective tissue within fascicles surrounding individual muscle cells.
- Identify where motor nerve terminals associate with skeletal muscle fibers and describe the distribution of cells innervated by one motor neuron in a muscle.
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- Discuss the physiological and biochemical basis of skeletal muscle contraction, how contractile proteins work, and how they are regulated in skeletal muscle.
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- Describe the regulatory proteins; specifically where they are located and how they respond to changes in calcium concentration.
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- Starting with an action potential in a motor neuron, explain the processes required to have a skeletal muscle undergo a single contraction and relaxation (a twitch).
- AP innervates skeletal muscle via ACh released at muscle, binds AChR –> depolarization via VG Na channels –> AP.
- AP spreads in both directions.
- AP spreads down the length of the muscle cell and also into the muscle cell via t-tubules (invaginations of plasma membrane in contact with the SR).
- In skeletal muscle, DHPR = t-tubule VG Ca channel that is in direct contact with SR Ca channel (RyR).
- Depolarization of DHPR affects RyR and Ca released (no extracellular Ca necessary).
- In cardiac muscle, Ca necessary outside the cell because no physical contact between DHPR and RyR.
- AP causes Ca release via DHPR, this Ca activates the RyR channel –> calcium induced Ca release.
- Each myofibril wrapped in its own SR which in contact with t-tubule at the terminal cisterna and has a protein calsequestrin. ‘Triad’ region.
- Ca released from SR binds troponin and starts the contraction cycle.
- Response terminated by ATPase pumps, Na/Ca exchangers –> brings cytoplasmic Ca back to normal and muscle relaxes.
- Explain the reason for the transverse-tubule system (t-system) in skeletal and cardiac muscle and how the excitation-contraction coupling is accomplished in skeletal muscle.
See above.
Smooth muscle needs no coupling; cells are thin enough that Ca can diffuse into the cell (so no t-tubule or SR system).
- Describe the two major mechanisms for how skeletal muscle tension is graded and regulated, and the basis of muscle fatigue.
Major regulator of contraction is Ca in all 3 muscle types. Length is also important since contraction is based on overlap of myosin and actin.
If muscle stretched to the point of no overlap, no tension can be generated. Tension increases linearly as amount of overlap increases.
Grade tension by increasing frequency of AP till tetanic contraction achieved, or recruit additional motor units, or change the length of the muscle (minor factor).
In cardiac/smooth muscle cells, grade tension based on NT levels and muscle length.
Fatigue is reduced performance during prolonged/intense activity. Decreases force production and speed of contraction. Fatigue can be due to impairment at any point in the process, but most often, steps affected are propagation of AP to t-tubule, release of Ca from SR, effect of Ca on myofilaments interaction, and force generation.
High frequency stimulation K builds up and Na reduced = reduced AP amplitude or failure; can recover quickly.
More typical fatigue due to metabolic changes, like increase in inorganic phosphate and decrease in pH as phosphocreatine decreases and creatine and inorganic phosphate increase decreased Ca release and reduced force generated by muscle.
- Describe the length of a sarcomere in resting muscle, contractile muscle, and muscle that is stretched almost to the point of injury (tearing) and discuss how this addresses the ambiguity of the question - “what is the length of a sarcomere?”
Resting = 2.4 um. Contracted = shorter. Stretched = longer (3.5 um).
- Describe the molecular basis of skeletal muscle diversity (fast and slow fibers) and the value of having this additional complexity.
Each motor neuron innervates one muscle and a subset of fibers within it. Motor unit = motor neuron + muscle fibers it innervates. They all contract in unison. Fine movements = small motor units. Gross movements = large motor units. Small units recruited first and then use progressively larger ones to have fine control over a movement.
Cardiac and smooth muscle don’t need nervous innervation; they have innate excitability.
Skeletal fibers can be slow or fast; have different myosin types, different #s of mitochondria, different resistance to fatigue, and different speeds of contraction.
Slow fibers used for postural and maintained contractions. Red, high myoglobin.
Intermediate fibers are fast, with glycolytic and oxidative enzymes.
Fast fibers have high glycolytic content and are used for rapid bursts.
Satellite cells are stem cells produce new myoblasts. Repair muscle fibers until satellite cells are depleted or can’t keep up. (Cardiac muscle has no satellite cells). Smooth muscle repairs itself (cells de-differentiate and renew the muscle).
Exercising doesn’t add more muscle fibers, but rather increases the cross-sectional area of each cell (add new myofibrils).
- Describe the key structural and physiological features of cardiac muscle and how they are similar to and different from skeletal muscle (sarcomere, regulatory proteins, events involved in a single contraction and relaxation, response to injury).
Cardiac cells need Ca, generally have only 1 nucleus, are striated, and use sliding filaments. They have gap junctions (intercalated discs) to transmit electrical impulses. No stem cells so they create scar tissue when injured.
- Explain why smooth muscle appears smooth and describe the key structural and physiological features of smooth muscle and how they compare to skeletal and cardiac muscle (contractile proteins, regulation of contraction, cell organization).
Smooth muscle not striated (but still uses myofilaments). Innervated sympathetically and parasympathetically (though some use APs). Regulated by Ca but only have 1 nucleus. May or may not have SR, but don’t use t-tubules or troponins.
- Describe how the skeletal muscle develops (single cells going to multinucleate cells).
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