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134 Lec 2 Nd Long Exam Essay

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Muscle Tissue

General features
Composed of differentiated cells containing contractile proteins (actin and myosin) Actin – thin filaments
Myosin – thick filaments
Mesodermal origin except for the iris muscle (ectodermal origin) Mesenchymal cell  lengthening + synthesis of myofibrillar proteins  muscle cells Muscle cell = muscle fiber (myofiber)

Three types of muscle tissue
1. Striated voluntary muscle (skeletal muscle)
Location: attached to skeletons
Shape: elongated, cylindrical cells showing cross striations Nuclei: multinucleated (synicitium); peripheral
Contraction: quick, forceful, voluntary control
2. Striated involuntary muscle (cardiac muscle)
Location: in heart and roots of large blood vessels only
Shape: elongated, branched individual cells separated by intercalated disks Nuclei: uninucleate and central
Contraction: involuntary, vigorous, and rhythmic
3. Nonstriated involuntary (smooth/visceral muscle)
Location: lining the alimentary, respiratory, urogenital tracts, blood vessels, ciliary muscle of the eye, arrector pili Shape: spindle-shaped, elongated showing no striations under LM Nuclei: uninucleate and central

Contraction: weak, slow, and not subject to voluntary control No striations? Is there still actin and myosin? Yes there still is, but the arrangement is not overlapping; myosin lilitaw lang pag may contraction, disintegrates when there is none

Terminologies
Sarcolemma – plasma membrane
Saroplasm – cytoplasm
Sarcoplasmic reticulum – sER
Sarcomere – mitochondria
Myoglobin – hemoglobin

SKELETAL MUSCLE
Histogenesis
Mesoderm  mesenchymal cell  myoblast  myotubes
1) Retraction of long cytoplasmic processes
2) Fusion of myoblast to form multinucleated myotubes
3) Elongation of myotubes by incorporating additional myoblasts 4) Myofilaments accumulate in cytoplasm
5) Accumulated myofilaments  myofibrils
6) Displacement of nuclei and other components peripherally

Structure of a myofiber
Elongated, unbranched, cylindrical, multinucleated cells
Flattened nuclei at the periphery
Most organelles and the sarcoplasm near the poles of nuclei
Sarcoplasm: many mitochondria, glycogen granules and an oxygen binding protein called myoglobin Glycogen – source of glucose monomers which serve as source of production of ATPs Liver – other storage of glycogen

Accumulate lipofucsin pigment with age
Mature skeletal muscle fibers cannot divide
Since they are highly differentiated cells
Muscle hypertrophy – not due to increase in number of muscle cells; due to increase in mitochondria, capillaries, thickening of connective tissue

Ultrastructure of a myofiber
Nuclei – flattened; several per cell
Plasma membrane – sarcolemma
Transverse (T) tubule – continuation of plasma membrane; interiorizes action potential (generated in sarcolemma) – for sarcomere (found in myofibril, which is inside the cell) Cytoplasm
Myofibrils – elongated structure
Mitochondria
Glycogen
Myoglobin
sER – inside T tubule; storehouse for calcium
TRIAD (sarcotubular system) = T tubule + 2 cisternae of sER

Organization of skeletal muscle
Connective tissues
Epimysium – DCT surrounding entire muscle
Perimysium – surrounds the bundles of muscle fibers (muscle fasciculi) Endomysium – delicate layer of CT composed of basal lamina and reticular fibers that surround individual muscle fiber Role: transmit the forces generated by contracting muscle cell; also provides vascularization by capillaries and lymphatic vessels *myotendinous region: the insertion of collagen fibers of the tendon into the complex infoldings of the sarcolemma From gross to molecular level

Muscle
Muscle fasciculus
Muscle fiber
Myofibril
Long cylindrical filamentous bundles
Striations on entire muscle fiber results from lateral registration of sarcomeres in adjacent myofibrils Myofilaments

Striations
A-band (anisotropic – birefringent in polarized light)
Dark bands
Occupied by the thick filament (myosin) that overlap with thin filament (actin) I-band (isotropic – do not alter polarized light)
Light bands
Occupied only by the thin filament (actin)
Z-line – bisects the I-bands
Sarcomere – from one Z-line to the next (2.5m long)
Functional unit of skeletal muscle
H-zone – consisting only of myosin
M-line – represents lateral connections between adjacent thick filaments; contains creatine kinase Function: catalyzes the transfer of a PO4 group from phosphocreatine to ADP; thus supplying ATP for muscle contraction!

Thin filament
Thin filament = F-actin + troponin + tropomyosin
F-actin = 2 strands of helical G-actin in double helical formation Tropomyosin – long, thin molecule made of 2 protein chains forming filaments Troponins
TnT – strongly attached to tropomyosin
TnC – binds calcium ions
TnI – inhibits actin-myosin interaction

Thick filament
Myosin molecule – much larger complex
Several hundred myosin molecules form the thick filament

Muscle contraction
Initiated by binding of calcium to the TnC unit of troponin This exposes the myosin binding site on actin
Myosin head binds to actin and ATP breaks down into ADP, yielding energy, which produces a movement of the myosin head The bound thin filaments over the thick filaments
This sliding repeats many times during a single contraction  complete overlap  shortening of whole muscle fiber

Sliding filament theory (Hugh Huxley)
Overall changes
1) A-bands remain the same
2) I-bands shorten
3) H-zone disappears

Review: biochemistry of muscle contraction
Motor end plate
Acetylcholine
Acetylcholine receptor
Triad
Calcium ions
Troponin C
Actin active site
Acetylcholinesterase
Calsequesterin
1) Neurotransmitter released diffuses across the synaptic cleft and attaches to Ach receptors on the sarcolemma 2) Action potential generated is propagated along the sarcolemma and down the T tubules 3) Action potential triggers Ca2+ release from terminal cisternae of sER 4) Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed 5) Contraction; myosin cross bridges alternately attach to actin and detach, pulling the actin filament toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process 6) Removal of Ca2+ by active transport into the SR after the action potential ends 7) Tropomyosin blockage restored blocking actin active site; contraction ends and muscle fiber relaxes *as action potential travels through T-tubules, it triggers release of calcium

Sarcoplasmic reticulum and T-tubule system
T-tubule – finger-like invaginations of the sarcolemma
Terminal cisternae of the sER + T-tubule = sarcotubular system (triad) INTERIORIZATION OF ACTION POTENTIAL
CALSEQUESTERIN – sequesters the calcium back into the storehouse Where is the T-tubule located in skeletal muscle?
At the A-I junction

Reading assignment
Rigor mortis
Myasthenia gravis
Muscle hypertrophy
Muscle atrophy
Muscle fatigue

Muscle spindles
Encapsulated proprioreceptors (sense self) within the belly
A type of proprioreceptor (“sense self”) a sensor in the muscle that identifies location of body parts e.g. close your eyes and move your arm (you still know where it is located because of muscle spindle) Consist of CT capsule surrounding a fluid-filled space (long, thick muscle fibers + some short thinner fibers = intrafusal fibers) Sensory nerves – monitor stretch in the non-contractile region of the spindle and send impulses to the CNS Motor nerves send impulses to adjust the degree of contraction in the intrafusal and extrafusal fibers Why important? To prevent overstretching

Nerve fibers penetrate the spindle where they detect changes in length of muscle fiber and relay this info to the CNS (esp. when moving or shifting body position) Function: controls the degree of contraction of opposing skeletal muscle e.g. body posture or position

Golgi tendon organs
Proprioreceptors at the origins and insertions
A fusiform structure (1mm long) situated at transition between skeletal muscle fibers and tendon fibrils Made of CT sheath encapsulating several large bundles of collagen fibers that are continuous with collagen fibers that make up the myotendinous region Function: to sense muscle tension when a muscle is contracted, sending signals to the brain about how much force is being exerted and where “protect the muscles, tendons, and ligaments from injury”

In short, muscle spindle detects change in muscle length (degree of stretch) of body parts  para malaman mo yung location ng kamay o paa mo Golgi tendon organs – detects degree of muscle tension para di ka mabalian!!!

Types of muscle fibers
Based on morphology, histochemistry, and biochemistry differences

Type I
Type II

Slow-twitch fibers
Fast-twitch fibers

Rich in sarcoplasm

Color
Myoglobin (dark red color)
Less myoglobin (light red color)
Diameter
Small
Large
Contraction
Continuous, slow
Discontinuous, fast
ATP
Slow
Fast
Metabolism
Aerobic
Anaerobic
Rate of fatigue
Slow
Fast
Sport
Endurance
Burst of power

Cross country
Weight lifting

CARDIAC MUSCLE
Histogenesis
Mesenchymal cells  align into chainlike arrays  complex junction in muscle between the cell (NO FUSION!!!) 1) Mesenchymal cells of primitive heart tube align
2) Cells within a chain often BIFURCATE and bind to cells in adjacent chains 3) As development proceeds, myofilaments accumulate in cytoplasm

Structure of cardiac muscle cell
Shape: elongated, cylindrical, branched
Size: 15m diameter and 85-100m length
Nucleus: 1-2 elongated central nuclei
Sarcoplasm: many mitochondria (lie in chains between myofilaments); lots of glycogen granules More mitochondria compared to skeletal muscle
More glycogen for continuous supply of ATPs
Arrangement of myofilaments yield a pattern of striations similar to skeletal muscle

Structure of cardiac muscle fibers
The sarcotubular system
1. The T-tubule and sER are not as regularly arranged
2. Triads are not common since T-tubules are generally associated with only one sER expansion. Thus, dyads only! 3. T-tubules are larger and more numerous
4. T-tubules at the level of Z line rather than A-I junction 5. Discrete myofibrillar bundles are not present
The mitochondria
40% or more of cytoplasmic volume  needed for continuous aerobic metabolism in heart muscle >2% in skeletal muscle
Intercalated disk
Dark-staining transverse lines
Represents 3 junctional complexes at the interface between adjacent cells arranged in stepwise fashion

Component
Function
Fascia adherens (similar to zonula adherens; half Z-line found in the vertical portion of the step. With alpha actinin anchoring thin filaments) Anchoring sites for actin!
Macula adherens (second component of transverse portion of a step) Prevents detachment of the cardiac cells from one another during contraction Gap junction (comprise the horizontal or lateral portion of the step) Provide electronic coupling between adjacent cardiac cells and (2) pass the stimulus for contraction from cell to cell

Types of cardiac muscle cells
Atrial cardiac cells
Ventricular cardiac cells
Smaller cells
Larger cells
Few T-tubules
More T-tubules
With small membrane-delimited granules containing ANF (atrial natriuretic factor for lowering blood pressure) No granules

SMOOTH MUSCLE
Histogenesis
Mesenchymal cells  in walls of developing hollow organs  cells ELONGATE and accumulate myofilaments  SMOOTH MUSCLE

Structure of smooth muscle cell
Shape: elongated, spindle-shaped
Size: 20-500m diameter
Nucleus: single, central ovoid nucleus
Sarcoplasm: many mitochondria; some rER, and a large Golgi complex Each fiber produces its own basal lamina and reticular fibers New discovery!!! Before, only epithelial cells have basement membrane/basal lamina The narrow part of one cell lies adjacent to the broad parts of neighboring cells

The myofilaments
No striations due to different arrangement of myofilaments compared to skeletal and cardiac Actin – lilitaw, lulubog; disintegrates into cytoplasm; attached to dense bodies, in turn associated with sarcolemma (along with intermediary filaments) Thin filaments

Actin filaments similar to those of the other 2
ALWAYS present in the sarcoplasm
ANCHORED in dense bodies associated with plasma membrane
Anchoring sites for actin
Skeletal – Z-band
Cardiac – fascia adherens
Smooth – dense bodies
Thick filaments
Myosin filaments less stable
NOT ALWAYS PRESENT but appear only in response to contractile stimulus Organization of myofilaments
Run mostly parallel to long axis of muscle fiber
Less regular arrangement  absence of striations

The sarcoplasmic reticulum
Poorly organized sER
Contain membrane-limited vesicles called caveolae  aid in calcium uptake and release No tubules and no dyads or triads!!!

Types of smooth muscle fibers
Parameter
Visceral SM
Vascular SM
Iris SM
Origin
Splanchnopleural mesenchyme
Mesenchyme developing around blood vessels
Ectoderm
Location
Walls of hollow thoracic, abdominal, and pelvic organs of respiratory, digestive, urinary, and reproductive systems Blood vessel walls (tunica media)
Eye (regulates entry of light)
Intermediate filaments (all kinds contain thick and thin filaments) Desmin
Vimentin, desmin
Vimentin, myomesin
Class
Unitary
Unitary
Multi-unit (cells can contract individually)

Organization of smooth muscle
Smooth muscle fibers do not abut end to end but overlap to varying degrees Muscle fibers attach to one another by FUSING their endomysial sheaths Smooth muscle also form fascicles that vary in size and organized in layers each fascicle surrounded by perimysium Thicker epimysial CT surrounds layers of fascicles

Mechanism of contraction
Initiation: influx of calcium
Calcium + CALMODULIN (calcium binding protein)
The complex activates the myosin light chain
Phosphorylated myosin light chain slides with actin
Cell contracts
Is there troponin C? NOOOOOO
Instead, there is calmodulin
Continued contraction involves formation of more myosin filaments and further sliding of the actin filaments The sliding of the actin pulls the attached DENSE BODIES close together, shortening the cell During relaxation, myosin filaments decrease in number and believed to be disintegrated into soluble cytoplasmic components

Response of muscle to injury
Depends on muscle type
Wound-close mechanism
Proliferation of fibroblasts in the perimyseal and epimyseal CT Synthesis of CT matrix materials
Skeletal muscle
Satellite cells (small mononucleated cells scattered in adult skeletal muscles within the basal lamina of the mature fibers) Mature fibers cannot divide
Quiescent satellite cells stimulated to divide
Satellite cells divide (muscle injury)  myoblasts  fusion to form new muscle Cardiac muscle
Little regenerative ability beyond early childhood
Lesions of adult heart  connective tissue scars
Smooth muscle
Proportion of undifferentiated mononucleated muscle precursors proliferate and differentiate  new smooth muscle fibers Same mechanism with uterus enlargement

NERVOUS TISSUE
The nervous system
Most complex system
More than 100 million nerve cells (human) and assisted by many more glial cells Each neuron  thousand interconnections with other neurons Neurons  grouped as circuits
Usually 2 or more circuits interact to generate a neural function!

Functions of the nervous system
By creating, analyzing, identifying, and integrating information, the NERVOUS SYSTEM generates two great classes of functions: 1. Stabilization of intrinsic conditions (e.g. blood pressure, O2 and CO2 content, pH, glucose levels, and hormones) with normal levels 2. Modulation of behavioral patterns (e.g. feeding, reproduction, defense, interaction with other living creatures) *protoplasm of nerve cell: highly excitable and conductive

inside is more negative, compared to outside; polarity (measured in millivolt) is responsible for excitability

Nervous tissue
Nerve cells (neurons)
Neuroglial cells (glial cells)

Histogenesis
Notochord  neurulation sends chemical signals to neural ectoderm = induction  neural ectoderm differentiation (neural plate)  neural fold & neural groove  neural tube = embryonic/rudimentary nervous system  (brain + spinal cord) all cells of the CNS

Neural crests – cells lateral to the n...

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