1. Muscle Histology and Cell Biology Flashcards
Introduction to Muscle Tissue
• Specialized for contraction:
– Energy from the hydrolysis of ATP is transformed into mechanical energy.
• Composed of ____ cells: known as skeletal muscle cell, muscle fibers, myofibers or myotubes.
• Characteristics of muscle:
– ____ - responds to stimuli (e.g., nervous impulses)
– ____ - able to shorten in length
– ____ - stretches when pulled
– ____ - tends to return to original shape and length after contraction or
extension
• Functions of muscle:
– Motion
– Maintenance of ____
– ____ production
elongated excitability contractility extensibility elasticity
posture
heat
Classification of Muscle Tissues
Two modes of control: voluntary (____); involuntary (____ and ____)
Skeletal/cardiac > ____; visceral > ____
skeletal cardiac visceral striated smooth
I. Skeletal Muscle
• Usually associated with bones:
– With some exceptions: e.g. ____.
• Induces movements:
– Large and forceful: e.g. walking, running, lifting movements.
– Small and delicate: e.g. manipulation, eye movements.
• Contraction duration:
– Long-term contractions, resistant to fatigue: e.g. ____ muscles.
– Rapid contractions, prone to fatigue: e.g. ____muscles.
• Secondary function: ____ production (e.g. shivering).
• Externally controlled:
– No contraction without ____.
– Voluntary control.
• ____ appearance.
These two types of movements is dependent on how many ____ are innervating (large and forceful vs. small and delicate)
Maintain internal temp > muscles are induced to contract (shivering) without exerting ____; rapid contraction > a lot of consumption of ____ > results in a production of heat; even though skeletal muscle is voluntary, it also has an ____ component > we do not directly control how much we shiver
tongue postural limb heat nerve signal striated
fibers
tension/movement
involuntary
Skeletal Muscle Cells
I. Muscle cell or fiber:
– Cylindrical cell 10-100 ____ in diameter, up to 30
____ in length.
– Multiple ____ nuclei; many ____.
– Plasma membrane or ____.
– Cytoplasm (or ____) with striations:
• ____ (80% of volume, striated).
• Sarcoplasmic reticulum (ER), T tubules.
• ____ for energy storage, ____ for O2 storage.
– Basal lamina:
• Connects ____ and maintains integrity of the tissue.
• Helps to transmit ____ generated by the muscle cells.
II.Satellite cell.
Cytoplasm of each cell is filled with bands of striated material > myofibrils (modifications of the cell’s ____ that provides the contractile force) > the nuclei are pushed to the side (located at the periphery of the cytoplasm)
The cells are ____ (cell that arises from the fusion of many cells) > results in multiple nuclei and mitochondria (very rich in energy)
Structure of sacroplasmic reticulum is much different from the ____
Muscle cells are surrounded by the basal lamina (epithelial cells also produce) > rich in ____
um cm peripheral mitochondria sarcolemma sarcoplasm myofibrils glycogen granules myoglobin
adjacent cells
forces
cytoskeleton
sintitial
normal ER
protein (laminin)
Skeletal Muscle Cells
Cross-section image > you can see that each cell has a ____ phenotype (the nuclei of muscle fibers is ____ than the satellite cell)
tubular
lighter
Skeletal Muscle Cell Structure
Striations: \_\_\_\_ in the muscle cell cytoplasm (sarcoplasm). Visible with \_\_\_\_. Alternating thick and thin filaments: • \_\_\_\_ bands, mainly myosin. • \_\_\_\_ bands, mainly actin.
Using polarized light you see two types of bands: A bands (anisotropic; thick filaments; has to do with how they refract light, and a reflection of the ____ structure of the bands); made up mostly of myosin; I bands (isotropic; thin filaments; absorb light differently, it passes through); made up mostly of actin
myofibrils
light microscopy
A (anisoropic)
I (isotropic)
molecular
Skeletal Muscle Cell Structure
• 80% of sarcoplasm occupied by myofibrils surrounded by ____.
• Two types of myofilaments make the myofibrils:
– thin ____ filaments.
– Thick ____ filaments.
• I + A bands = ____,
contractile unit of skeletal muscle.
• One sarcomere extends between adjacent ____ (lines or bands).
Viewing via ____ microscopy
Bands correspond to Z disk; this is where the I band is actually located (____ electron dense area in E microscopy; appears lighter in light microscopy); the ____ electron dense area between Z disks > corresponds to the A band
We see that the muscle cell is organized in such a way in that there is a bunch of functional repeats of sarcomeres; is the area between two Z disks [functional unit of myofibrils, structural unit of myofibril?]; myofibril is the repetition of multiple ____
mitochondria actin myosin sarcomere Z disks
electron
less
more
sarcomeres
The Sarcomere
• Myofibrils are repeats of ____ units.
• I band:
– ____ – major component; two protein strands twisted around each other, contain “____”.
– Other proteins – Tropomyosin, Troponins, Nebulin.
• A band:
– Myosin - flexible “heads” with ____
activity protrude outward (except at ____), attach to “active” sites on actin (thin) filament.
– H band – contains ____; forms ATP.
– M line – located in ____ of the H band; provides ____ to myosin filaments.
• Z-disk (Z-line, Z-band) – where ____ filaments attach; mostly ____.
In the center of the A band > H band (electron ____ area) > rich in creatine kinase (carrier of ATP from mito into contractile system; can only contract if there is enough ATP (produced at mito)
Myosin filaments organized in ____ > two tails meet at the ____ line
This whole structure contracts when the muscle contracts
sacromere actin active sites ATPase filament center creatine kinase middle structural support thin alpha-actinin
dense
tail-to-tail configuration
M line
Mechanism of Skeletal Muscle Contraction: Molecular Components – Thin Filaments
• ____:
– Major component of the thin filament.
– Double-stranded, twisted polymer of globular (____) monomers.
– ____, with plus (+) and minus (–) ends.
– The ____ end inserts into the Z disk.
F-actin
G-actin
polarized
plus
Mechanism of Skeletal Muscle Contraction: Molecular Components – Thin Filaments
• Tropomyosin:
– Two ____ chains twisted around each other
forming a thin strand.
– Located in the ____ of F-actin strands, covering
active sites.
– Binds the troponin complex.
• Troponin complex:
– Makes skeletal muscle contraction responsive to ____.
– Three proteins:
• Troponin T: binds the complex to ____.
• Troponin I: ____ binding of myosin to actin.
• Troponin C: binds ____ (unique to ____ muscle).
Tropomyosin (pink) > long fibrillar proteins that are embedded in groove of actin filament; binds actin complex and prevents the binding of myosin at active sites (prevents interaction with ____ filaments)
identical groove Ca2+ tropomyosin inhibits Ca2+ skeletal
thick
Mechanism of Skeletal Muscle Contraction: Molecular Components – Thick Filaments
• Composed of numerous myosin protein strands. • Myosin: \_\_\_\_ activity. Binds \_\_\_\_ to F-actin. Two heavy chains: • \_\_\_\_: self-assembly region. • Globular head: – Flexible, protrude outward all around filament (except center). – \_\_\_\_ and \_\_\_\_ domains.
Two pairs of light chains:
• Essential light chain.
• Regulatory light chain.
Two types (depending on ____):
• Fast Myosin
• Slow Myosin
____ > two myosin molecules that have two domains (head and tail); tails form a twisted chain; heads protrude away from tails
Myosin light chains (____); ATPase carried out by head of heavy chain of myosin; change in conformation allows head of myosin to interact with actin (binding domain is here)
When myosin filament is assembled > ____ ends of tails self-assemble (similar to collagen) > where the thick filament is thicker (corresponds to ____ of sarcomere)
ATPase reversibly tail actin-binding ATPase
ATPase rate
heterodimer
regulatory
C terminal
M line
Mechanism of Skeletal Muscle Contraction: Other Components
• Nebulin: – Inserts into \_\_\_\_. – Regulates \_\_\_\_ length. • Titin: – \_\_\_\_ protein in animal kingdom (up to 34,350 aa; MW 3.8 × 106). – Associates with \_\_\_\_ and inserts into the Z disk, reaching to the \_\_\_\_. – Highly \_\_\_\_: muscle recoil. • Myomesin, C-protein: – Crosslink \_\_\_\_ and \_\_\_\_.
Nebulin solves the problem of how long the thin filament has to be > actin filament grows to the point at which there is no more ____ (the end of nebulin marks the maximal length of the thin filament)
Titin (purple) > extends from Z disk to M line; myosin thick filaments associated with titin; after contraction of sarcomere, titin gets compressed (very elastic protein); when stimulus to contract disappears, titin relaxes itself and returns the sarcomere to its ____; cell doesn’t need any ____ to return back to its original length (due to the elastic recoil of titin)
Z disks thin filament largest thick filaments M line elastic myosin titin
nebulin
original length
energy
The T-tubule System and the Sarcoplasmic Reticulum
• Transverse-tubule system:
– Invaginations of the ____ around the
myofibrils.
– ____ open into the sarcoplasm: pass through
and open somewhere else on the sarcolemma (i.e., these tubules are not used to get things into and out of the muscle cell).
– Conduct ____ from the surface of the cell (sarcolemma) down into the SR.
• Sarcoplasmic reticulum (SR, muscle cell ER):
– Terminal cisternae and longitudinal tubules.
– ____ storage for muscle contraction.
SR > specialized form of regular ER; original function of normal ER is to produce secretory proteins and to transport to the Golgi; in SR, in addition to the ____ function > serve as a huge storage place of Ca2+ > Ca2+ needs to be liberated from SR in proximity of microfilaments in order for contraction to take place
sarcolemma
NOT
electrical impulse
Ca2+
regular
The T-tubule System and the Sacroplasmic Reticulum
For contraction to occur, the nerve cells must induce electrical activity at level of ____ at skeletal muscle cell > the activity releases the Ca2+ from the SR, the activity (electrical impulse) travels across via the ____ (essentially a continuation of the PM) to the SR
PM
T-tubule
The T-tubule System and the Sarcoplasmic Reticulum
• Triad: – Site of contact of the T tubule with the \_\_\_\_ of the SR. – Two \_\_\_\_ of the SR and a central \_\_\_\_. • In human skeletal muscle, each sarcomere has \_\_\_\_ T-tubules running \_\_\_\_ to the fiber.
Configuration of the SR (cisternae > ____ of SR) is ____ (remains constant) > for each T-tubule we find two cisternae > triad; for each sarcomere, we will find ____ triads per sarcomere > makes transfer of ions from cisternae of SR towards myofilaments very efficient
In ____ there are no triads, they are actually diads (difference bt cardiac and skeletal muscle)
cisternae lateral sacs T tubule two perpendicular
vesicles
fixed
two
heart
Mechanism of Skeletal Muscle Contraction: Sliding Filament Model
Contraction: muscle shortens up to ____ of resting length.
During contraction:
- Constant distance between ____ and the edge of ____.
- Reduction in length of ____ and ____.
1/3 Z disk H zone H zone I band
Mechanism of Skeletal Muscle Contraction: Sliding Filament Model
• Sliding filament model:
- Constant distance between ____ and the edge of ____ → No change in length of thin and thick filaments
- Reduction in length of ____ and ____ → Length of sarcomere decreases.
- The contraction force is generated by the process of moving one type of filament past the adjacent filament of the other type.
Z disk
H zone
H zone
I band
an analogy for sarcomere: a tug-of-war
teams face ____ from each other
away
Anchorage of the Muscle Cell to the Basal Lamina
• Network around myofibrils to protect from mechanical stress.
• Organization:
– Desmin:
• ____ filaments linking myofilaments to the
sarcolemma.
– ____:
• Reinforces the sarcolemma by linking to the ECM- binding dystroglycan complex.
– Dystroglycan complex:
• Receptor for ____.
• Links dystrophin to the ____
intermediate
dystrophin
laminin-2
ECM
Anchorage of the Muscle Cell to the Basal Lamina
In addition to myofilaments > specialized system to transmit forces from myofibrils to the PM, and from PM to the outside ECM > the cell contracts against something
The system is not more than the regular modification of the ____ of the cell
**Dystrophin > large protein capable of interacting with ____ filaments (not part of the sarcomeres, but attached to it) and interacts with the dystogycan complex > interacts with laminin in basal lamina
When contraction of myofilaments, force goes through cytoskeleton of cell, then to the PM which is anchored to ____ molecules in BL > two effects: place against which the force of contraction can be used, and the complexes/cytoskeletal elements provides a way for the cell to not have its sarcolemma from being disrupted
cytoskeleton
actin
laminin
Anchorage of the Muscle Cell to the Basal Lamina: Dystroglycan
• \_\_\_\_ receptor. • \_\_\_\_ and \_\_\_\_ subunits. • Regulates laminin polymerization → \_\_\_\_ formation. • Laminin-DGC provides stability to the \_\_\_\_ during muscle contraction.
Mutations in gene for dystrophin > cause of ____ (muscle failure and inability of cell to interact with molecules in ECM)
laminin transmembrane (beta) extracellular (alpha) basal lamina sarcolemma DMD
Satellite Cells
• Located between ____ and ____.
• Myogenic precursor cells:
– Usually ____.
– Proliferation in response to stress and trauma (____).
A type of ____ > can be induced to divide and form new muscle cells (following damage, repair, or hypertrophy following exercise)
basal lamina sarcolemma quiescent muscle repair stem cell
Organization of the Skeletal Muscle
• Muscle cell or fiber:
– Elongated syncytium.
– Enveloped by the ____: thin CT.
• Muscle fascicle (bundle):
– Bundle of muscle cells.
– Surrounded by the ____: derives from the epimysium.
• Muscle (organ):
– Bundles of fascicles.
– Surrounded by ____: dense CT.
Outside of BL of myofibrils > layer of thin connective tissue > endomysium (presence of ____ in this area)
endomysium
perimysium
epimysium
fibroblasts
The Myotendinous Junction (MTJ)
Specialized region connecting skeletal muscle (M) to tendon (T): ____ unit.
– Tenocytes (tendon cells) produce collagen fibers anchored to the ____ of the muscle cell.
– Sub-sarcolemmal densities (____) at the T tips of the Flp connect ____ filaments from
the last Z-band to ____ in the tendon
ECM.
integrated mechanical unit finger-like processes (flp) alpha-actinin actin laminin
The Myotendinous Junction (MTJ)
____ connect muscle to bone
Skeletal muscle contracts and generates tension on tendon (must be a deep connection between the two); structure of sarcomeres stop at the last ____
In the Flp region (apical end of muscle cell) > the sarcolemma is highly digitated with the ECM of the tendon > at the tips of the digitations: ____ (Ssd, aggregations of same protein that makes Z disk, alpha-actinin)
At last Z disk there are ____ filaments that connect to the Ssd; the densities are associated with receptors located at the level of the PM (like dystrophin, etc.) that interact with ECM of tendon > force is now transmitted (tension is distributed through actin filament, to Ssd, to the ECM of the tendon)
tendons
Z disk
sub-sarcolemmal densities
actin
The Neuromuscular Junction (NMJ)
• Nerves transmit a membrane depolarization signal (action potential; to be studied in BS-IV) to the skeletal muscles that induces contraction.
• ____: The parent motor nerve and all the muscle fibers that it innervates.
• Neuromuscular junction:
– Specialized synapse between a motor
neuron and a muscle fiber.
– Synthesis and release of the
neurotransmitter ____, in response to action potentials.
Functional unit of one nerve and muscle fibers it contacts > motor unit; at the end you see the axon of the nerve changes ____, forms a specialized synapse > NMJ
motor unit
acetylcholine (ACh)
morphology
The Neuromuscular Junction: The Motor End Plate
Nerves branch into a root-like structure; and formation of the motor-end plate > region of ____ (PM of cell) that is infolded > very intimate contact between the terminal of ____ and the ____
sarcolemma
nerve axon
muscle cell
The Neuromuscular Junction: The Motor End Plate
Motor end plate:
Region of the sarcolemma in closest proximity to the ____.
____ synaptic clefts: depressions of the muscle fiber formed by invaginations of the sarcolemma.
____ synaptic clefts: deeper junctional folds, with ____ receptors.
NTs are produced at this level
axon end terminal
primary
secondary
The Neuromuscular Junction
• Fine motor control
from few fibers: (~____ fibers/motor unit)
• Powerful movements
from large numbers: (~____ fibers/motor unit)
Depending on how many fibers are innervated by nerve determines the ____ of the muscular activity
5
100
control
Slow and Fast Muscle Fibers
• Slow-twitch* or \_\_\_\_ (\_\_\_\_ meat): – Slower response to nervous stimulation. – \_\_\_\_ diameter. – Well \_\_\_\_. – Rich in \_\_\_\_ and myoglobin. – More \_\_\_\_ than fast-twitch.
• Fast-twitch or \_\_\_\_ (\_\_\_\_ meat): – Respond \_\_\_\_ to nervous stimulation. – \_\_\_\_ diameter. – Fewer \_\_\_\_. – Fewer and smaller \_\_\_\_ than slow-twitch. – Easily \_\_\_\_
• Distribution of fast-twitch and slow twitch:
– Most muscles have both but varies for each muscle.
*Twitch: Muscle contraction in response to a stimulus.
high-oxidative red smaller vascularized mitochondria fatigue-resistant
low-oxidative white rapidly larger blood vessels mitochondria fatigued
Slow and Fast Muscle Fibers
Slow-twitch > contract slowly for long periods of time if stimulus is constant > need a mechanism to obtain energy in an efficient way for long time > highly oxidative > main source of energy is ____ when burning glucose > very rich in mito and accumulate high cxn of oxygen by being rich in protein myoglobin (monomer) > what makes the fibers more red (dark meat)
Fast-twitch > poor in myoglobin and mito > but can respond rapidly; and have a myosin that is slightly faster than the myosin found in thick filaments of slow-twitch > metabolism is based on ____ > run out of energy rapidly > not resistant to fatigue
ox phos
anaerobic glycolysis
