2-5. Skeletal Muscle Structure & Function Flashcards
What is the hallmark of all living organisms?
Ability to use energy
What is ATP? Where is it found? In what amounts?
- Energy currency found in all cells
- In small amounts ranging from 3-6 mmol/kg in skeletal muscle
How many skeletal muscles are there in the body?
660
What percentage of body weight does skeletal muscle make up?
45%
What is the primary function of skeletal muscle?
Force generation
What are the secondary functions of skeletal muscle?
- Heat production
- Glucose uptake and storage
- Regulation of metabolic rate
- Source of fuel (amino acids, esp in starvation)
How does skeletal muscle aid in heat production?
- Body is inefficient at converting substrates into energy
- Vast majority is lost as heat
- Muscles help maintain body temp
What happens when skeletal muscles don’t utilize glucose?
- Muscle is a primary utilizer of glucose
- When sedentary & not utilizing glucose, peeps get glucose regulatory conditions like diabetes
What is a muscle composed of? Percentages?
- 75% water
- 20% protein
- 5% other
List and describe the cellular components of muscle?
- Contractile tissue = myosin, actin
- Connective tissue = tendons, fascia
- Vascular tissue
- Neural tissue = motor innervation & sensory receptors
What are the sensory receptors of muscle?
- Muscle spindle
- Golgi tendon organs
- Mechanoreceptors
- Nociceptors
What are the cellular organelles contained in each myocyte?
- Multiple myonuclei
- Mitochondria
- Ribosomes, Golgi Apparatus, Endoplasmic Reticulum
Why are nuclei generally lie on the external/peripheral surface of a muscle cell?
To avoid “machinery” pumping in the middle of muscle cells during contraction
What are the unique features of skeletal muscle?
- Multinucleated
- Capable of regeneration
- Very adaptable
Why are muscle cells multimucleated?
Diffusional efficiency
How many nuclei per cubic mm are there in each muscle cell?
200-300
How are muscle fibers adaptable?
- Can modify their metabolic properties in response to alterations in use
- Can alter their size throughout life in response to various stressors
What muscle cells are capable of regeneration?
Satellite cells
What are the 3 types of connective tissue sheathes of a muscle cell? What does each cover?
- Epimysium covers the whole muscle
- Perimysium covers the fascicles
- Endomysium covers the individual muscle fibers
What are the 2 membranes that surround each muscle fiber? Which is semi-permeable?
- Sarcolemma = plasma membrane, semi-permeable lipid bilayer (inner)
- Basal lamina = basement membrane (outer)
What is the cross-sectional area of a muscle fiber determined by? What is the range?
- Number of myofibrils
- 2000 - 7500
What is the range of muscle fiber length?
3-4 mm to 30cm
What is a satellite cell? Location? Allows for what following injury? Why is this property is lacking in the heart?
- Undifferentiated nuclei
- Between sarcolemma & basal lamina
- Provide regenerative potential
- Lacking in heart so it doesn’t grow too large b/c of training
What percentage of all nuclei are satellite cells?
5-15%
What kind of nucleus are myonuclei? Location?
- Post-mitotic
- Beneath (inside) sarcolemma
- Periphery of muscle fiber
What are the functions of mitochondria?
- Production of ATP to drive cross-bridge formation
- Role in maintenance of muscle force during prolonged contractions
Where are mitochondria located in a muscle fiber?
- Intermyofibrillar = between myofibrils
- Subsarcolemmal = below sarcolemma
What are the key markers of mitochondria?
- Succinate dehydrogenase
- Citrate synthase
- Cytochrome C
What makes up the macrovasculature of skeletal muscle?
- Arteries
- Veins
What makes up the microvasculature of skeletal muscle?
- Arterioles
- Venules
- Capillaries
What is an aspect of blood flow that only occurs at the levels of the capillaries?
Exchange of gases, nutrients and metabolites between the blood and the tissues
What makes up a muscle microvascular unit?
- One terminal arteriole
- 2 collecting venules
- 15-20 capillaries
How many muscle fibers does one microvascular muscle unit serve?
20-30
What do the major features of sarcomeres look like under light microscopy?
- A bands = dark, wide
- I bands = lighter, wide
- Z line = dark, thin, bisects I bands
What are the major features of a sarcomere?
- Z line = anchor for thin filaments
- M line = anchor for thick filaments
- A band = all myosin (w/ overlap)
- I band = only actin
- H band = only myosin
During a contraction, how do the sizes of bands in a sarcomere change?
- Overlap increases → lose areas that are single filament type → I band (actin), H zones (myosin) decrease
- A band doesn’t change b/c length of filaments doesn’t change
What is the ratio of myosin to actin where they overlap in a sarcomere?
6 actin : 1 myosin
What are the proteins associated w/ the sarcomere?
- Contractile proteins
- Regulatory contractile proteins
- Structural & costameric proteins
What is the role of contractile proteins? Examples?
- Force generation
- Myosin, actin
What is the role of regulatory contractile proteins? Examples?
- Turn the contractile apparatus on/off
- Modulate activity of MHC
- Tropomyosin, troponins, MLC
What are the functions of structural and costameric proteins?
- Maintain adjoining sarcomeres in alignment
- Maintain alignment of thick and thin filaments
- Mechanical linkage between sarcomere and extracellular matrix (endomysium)
What is the protein makeup of a thick filament?
- Mostly myosin
- 2 MHC
- 4 MLC
What are the 2 functions of the MHC globular head.
- Actin binding site
- ATPase activity
What are the proteins of thin filaments? Which are regulatory?
- Actin = only non-regulatory
- Troponin
- Tropomyosin = inhibitory (TnI), calcium (TnC), tropomyosin (TnT)
Why can’t a sarcomere expand outwardly toward the Z line with force?
Myosin heads (MHC) only contract towards the center of a sarcomere
In a sarcomere, how do the regulatory proteins (troponins & tropomyosin) control exposure of the action-myosin binding site?
- Tropomyosin directly blocks binding sites
- TnI = keeps whole troponin complex in place
- TnC = binds calcium to move tropomyosin out of the way when needed
- TnT = keeps tropomyosin in place
What 2 sarcomeric proteins co-ordinate the “tracking” of actin and myosin?
- Nebulin
- Titin
What 2 structural proteins maintain “registry” and force transfer between sarcomeres? Location?
- Alpha-actinin
- Desmin
- Both anchored @ Z line
Which protein contributes to passive (recoil) tension in muscle?
Titin
What are the functions of the cytoskeleton?
- Has additional structures that facilitate the force generating function of the myofilaments
- Involved in the alignment of the thick and thin filaments
- Transmission of force from the sarcomere to the skeleton
What are costameres?
- Sites of mechanical linkage between sarcolemma and basal lamina
- Contains dystrophin –> lack of which causes muscular dystrophy (cells rip themselves apart b/c not connected to one another)
Describe the phenomenon of lateral force transmission in endomysial matrix.
EXPERIMENT A:
-anchored single fiber extending from muscle on both ends
-untethered fibers remain unanchored
-stimulated anchored fiber
-single fiber tetanic tension
EXPERIMENT B:
-anchored one end of extended muscle fiber and 2 ends of untethered fibers
-stimulated extended fiber only anchored on one end
-get the exact same force production as experiment A
What are the results of endomysial matrix? Significance?
- Force transmission occurs not only through serial connections of muscle fibers to their tendons at the ends of muscle fibers, but also through parallel (lateral) connections among adjacent muscle fibers contained w/in the endomysial matrix
- Allows for greater redundancy in force transmission
What does the Sliding Filament Theory propose?
- A muscle shortens or lengthens b/c the thick and thin filaments slide past each other, w/o changing length of filaments
- Sarcomere length changes
- The myosin cross bridges, which cyclically attach, rotate and detach from the actin filaments w/ energy from ATP hydrolysis
- This provides the molecular motor to drive fiber shortening
How does the length of the sarcomere change according to the Sliding Filament Theory?
- Decreased length of I band, H zone
- No change of length of A band
Explain the events that must occur before the cross bridge cycle.
-Ca2+ ions released from SR bind to troponin –> troponin changes shape –> tropomyosin unblocks binding site
Explain the cross bridge cycle
- Cross bridge formation = myosin head binds to actin
- Powerstroke = ADP released –> activated myosin head pivots –> thin filaments slides toward center of sarcomere
- Cross bridge detachment = ATP binds to myosin head –> link between actin & myosin weakens –> myosin head detaches from actin
- Reactivation of myosin head = ATP binds to myosin head –> ATP hydrolyzed to ADP & inorganic phosphate –> energy liberated from hydrolysis of ATP activates myosin head –> head assumes cocked position
What are sarcoplasmic reticulum cisterns? Relation to the T tubules?
- Invaginations of sarcolemma
- Located on both sides of T tubule
- Store calcium
How is the triad positioned relative to internal structure of a sarcomere?
Triad positioned where actin & myosin interact
What makes up the triad?
T tubule sandwiched between 2 sarcoplasmic reticulum cisterns
How is the level of intra-cellular calcium controlled within a muscle cell? How is it elevated? How is it lowered?
LOOKUP
Describe the process of excitation-contraction coupling.
- ACh released –> depolarizes muscle cell & triggers AP
- AP propagates into T tubule
- Depolarization of T tubule –> Ca2+ release from SR
- Ca2+ binds to troponin –> cross bridge cycle
- Contraction terminates when Ca2+ is pumped back into SR via ATP pump
How is the depolarization of the T tubule translated into release of calcium from the SR?
- At rest, DHPR on T tubule has a “plunger” component that mechanically blocks RyR on SR
- When activated by AP from motor neuron, T tubule becomes depolarized –> conformational change in DHPR –> RyR channel opens –> Ca2+ diffuses from SR to cytosol
- SR reuptake of Ca via ATPase
What are the 2 primary membrane proteins involved in calcium release from the SR?
- Dihydropyridine receptors = voltage sensitive calcium release channel
- Ryanodine receptors = calcium release channel
What are the roles of calcium in muscle cells?
- Initiation of muscle contraction
- Activation of cytoplasmic enzymes (GLUT4)
- Activation of mitochondrial enzymes (krebs cycle)
- Cell signaling for glucose uptake and regulation of fiber types
What makes up the total force developed by a muscle?
Sum of the forces generated by all of the cycling cross bridges
What does the number of simultaneously cycling cross bridges depend on?
- Frequency of muscle stimulation
- Initial length of the muscle fiber
What is tension? What does it do?
- Force exerted when a muscle is stimulated to contract
- Tends to pull attachments toward each other
Isometric vs. Concentric vs. Lengthening contraction
- Isometric = constant length, occurs when both ends of the tendons are fixed and immovable
- Concentric = shortening
- Eccentric = lengthening
What is a twitch?
Smallest contractile response to a single stimulus
How does the frequency of stimulation of a muscle control force generation?
- Frequency-tension relationship
- Higher frequency of stimulation = increased force generation
What is power?
Power = force x velocity
What muscular property is affected by altering the number of sarcomeres in series?
Velocity
What muscular property is affected by altering the number of sarcomeres in parallel?
Force
What is tetanus?
Response of muscle to repeated stimuli
Fused vs. Unfused tetany
- Fused = smooth tetany; no relaxation between stimuli
- Unfused = relaxation between stimuli
Explain the frequency-tension relationship.
- Force production depends on frequency of stimulation
- Higher frequency of stimulation = increased muscle tension
Explain the length-tension relationship. What does the graph look like? What happens at optimal length? Before? After?
- Relationship between length of muscle and force output
- Inverted U graph
- Optimal length = most force produced b/c maximal overlap of actin & myosin
- Before optimal length = actin overlaps in the middle of sarcomere w/o presence of myosin heads
- Past optimal length = no overlap between actin & myosin
What is passive force? When does it occur in a muscle?
- Occurs when muscle goes beyond optimal length
- Elastic component of muscle resists lengthening
What makes passive force different than active force?
- Doesn’t require neural activation
- Doesn’t come from cross bridge formation
What kind of movements do the force-velocity relationship describe?
Movement that aren’t at a constant muscle length
What kind of movements do the length-tension relationship describe?
Isometric contractions (constant length)
Explain the force-velocity relationship. Example?
- Describes force generated during isotonic contractions
- Velocity of muscle contraction depends on the force resisting the muscle
- Force & velocity inversely related
- Ex) biking uphill vs. downhill
What are isotonic contractions? When do they occur? Delay?
- Constant load
- Occurs when the whole muscle can shorten and lift a load of constant mass
- Latency period between when a muscle is stimulated and when the load moves
How does a muscle increase the number of fibers it can pack into a fixed volume?
Angle fibers in a pennate fashion
What is the result of having a greater number of fibers in a muscle?
More fibers in parallel = more force generated
On a force-velocity curve, what do we call the point where the curve crosses the y-axis? x-axis?
- y = Max. isometric force
- x = Vmax (max velocity of shortening)
For a force-velocity relationship, is eccentric maximal force greater than, less than, or equal to isometric Fmax?
Greater than
What factors control the max amount of force a muscle can produce?
- PCSA of fibers in parallel
- Length-tension relationship = overlap between actin & myosin
- Frequency of stimulation
What factors control the max velocity of shortening of a muscle?
- Myosin ATPase activity
- Length of muscle fibers (sarcomere in series)
Longitudinal vs. Pennate muscle. What is each specialized for?
LONGITUDINAL: -longer fibers w/ more sarcomeres in series -fibers run in direction of tendons -specialized for speed of contraction PENNATE: -shorter fibers w/ more sarcomeres in parallel -fibers run at angle to the tendons -greater PCSA -specialized for force production
Which muscle design has the greatest CSA?
Bipennate
Anatomical vs. Physiological CSA
- Anatomical = perp to line of pull of a muscle
- Physiological = circular area produced by length of muscle and A-CSA
How do you increase P-CSA?
Increase angle of muscle fibers
Fast vs. Slow twitch muscles w/ regards to myosin ATPase activity.
- Fast = high myosin ATPase activity
- Slow = slower rate of ATP hydrolysis by myosin ATPase
