Muscle: General Information
The major distinguishing feature of muscle cells is the ability to contract- when a muscle cell/fiber contracts they shorten some axis. Muscle fibers are typically arranged in parallel a myriad of cells/fibers can work in concert smooth muscle cells are typically arranged in layers, each with different orientations The ability of a muscle fiber to contract depends on the accumulation of particular intracellular proteins The majority of a muscle cell/fibers cytoplasm is occupied by contractile proteins, mainly: thin filaments (6-8nm, mostly actin) thick filaments (~15nm in diameter, myosin) No motility so no flagella/microvilli
Striated vs. Smooth Muscle
Striated: you can see cross striations at the LM level; alternation of light and dark bands forming sarcomeres
skeletal – attached to bone and moves the axial and appendicular skeleton
visceral striated – may have attachments to bone but is associated with the gut tube; same histology, but different embryology
cardiac – the heart
smooth: cells exhibit no cross striations found in the viscera [vessels, organs, glands] collection of cells (NOT FIBERS) arranged in layers; spindle shaped with nucleus within; sweat glands, goose bumps, visceral glands, etc.
Skeletal Muscle: Formation and Mature
muscle fibers arise from aggregations of myoblasts, these cells fuse giving rise to a muscle fiber a muscle fiber is a syncytium; a muscle fiber contains many nuclei (~35 per mm) that are situated directly beneath the plasma membrane (i.e. peripherally) a single muscle fiber may not course the length of the muscle the strength of a muscle depends on the number of fibers
•is characterized by myofilaments produce the typical cross-striation of muscle
•“A bands” – (dark bands that are bisected by H zone [M line bisects the H zone])
•“I bands” – bisected by Z line
A bands: where actin and myosin overlap
Space between A bands is the I bands (pale)
Line that run down the I bands = Z lines/discs
Sarcomere: Z line to Z line which is the functional unit of the muscle
Light microscope
Muscle Associated Connective Tissue
Skeletal muscle includes connective tissue components:
1.Tendons: made of DRCT bended to the periosteum where they attach
2.Coverings:
a.epimysium - surrounds the collection of fascicles that comprises the muscle; major structures penetrate this layer
b.perimysium - surrounds groups of fibers to form fascicle
c.endomysium: slight, delicate layer that surrounds individual muscle fibers
NOTE: Nerves and blood vessels travel in-between these connective tissue layers.
Layers of Muscle Connective Tissue
Muscle Tendon Junction
Blue: collagen fibers blending together with the muscle – beginning of a tendon
Cardiac muscle
Muscle Bone Junction
Lamellar bone with Haversian canals and Volkmann’s canals with osteocytes in lacunae
Middle: periosteum – bone muscle junction
Adipose tissue
Skeletal muscle
Transverse Tubules: Skeletal Muscle
The t-tubules are invaginations of the plasma membrane (also called sarcolemma).
The TRIAD: t-tubule in the middle and two things of sarcoplasmic reticulum
Sarcoplasmic reticulum = calcium storage spot (pink)
T –tubule – invagination of the plasma membrane and is surrounded by the sarcoplasmic reticulum – want it next to the calcium storage for depolarization
Red is the plasma membrane
Muscle Fiber Types
Skeletal muscle fibers differ in their diameter and color.
The different fiber types are attributed to myoglobin and mitochondria content.
Myoglobin is an oxygen binding protein that can “hold” oxygen until the cell needs it.
•White fibers
•Red fibers
•Intermediate fibers
Many ATPase = dark staining; light stains are less ATPase
The fibers are all different because they serve different functions
Lots of ATPase = red fibers and white fibers have little ATPase and intermediate have medium amount
White Fibers
White/fast fibers were adapted for rapid and powerful contractions
•fast twitch fibers, anaerobic, Type II & IIb
•larger fibers (= more strength)
•more extensive sacroplasmic reticulum
•large amount of glycogen and glycolytic enzymes for rapid energy, lower amount succinate dehydrogenase, ATPase
•less extensive blood supply
•fewer mitochondria
sprinting, jumping, short activity
succinate dehydrogenase - mitochiondrial enzyme, indicates the abundance of mitochondria
Red Fibers
Red/slow fibers were adapted for prolonged, continued activity
•slow twitch fibers, aerobic, Type I
•smaller fibers (smaller nerves)
•extensive blood supply
•many mitochondria and myoglobin
Myoglobin gives the red appearance; combined with oxygen and stores it until the mitochondria need oxygen
standing, sitting, long distance running
Myofibrils and Myofilaments
•myofibrils are the contractile unit of the muscle fiber
•a single muscle fiber will contain numerous arrangements of myofibrils
•myofibrils are composed of bundles of myofilaments
•myofilaments are composed of polymers of actin and myosin (as wells as numerous other proteins) and are the contractile elements of the fiber
•myofibrils are surrounded by a specialized SER, termed the sacroplasmic reticulum
Sarcomere
•is a subunit of the myofibril, measures 2-3 μm in mammals
•is characterized by cross-striations formed by the differing arrangements of thick and thin filaments
electron micrograph
A band: thick dark middle part with lighter line running throught it (M line)
I band: light sides with dark band running through it (Z line)
Myofilaments
•The thin filaments are composed of actin, tropomyosin and troponin.
•The thick filaments are myosin and are held in place by a sheet of myomesin (myomesin corresponds to the M line).
•Actin, myosin, troponin and tropomyosin make up about 75% of skeletal muscle protein.
•Other structural proteins:
–Titin – elastic protein, connects thick filaments to Z disc
–Nebulin – inelastic, attached to Z discs and parallels actin
–Actinin – bundles actin filaments into arrays and anchors
–Myomesin – holds myosin in register at M line
–C protein – myosin binding protein
–Plus many more…
Relaxed vs. Contracted Sarcomere
Changes during contraction:
1.Sarcomere shortens
2.I band shortens
3.A band is unchanged
4.H zone disappears
•the sacroplasmic reticulum, a modified smooth ER, is arranged around myofibers; serves as a reservoir for Ca++
•the t tubules are invagination of the plasma membrane, the fluid in them is extracellular
•the sarcoplasmic reticulum is also responsible for uptake of Ca++
Motor End Plates
The motor end plate is the axonal contact made onto a muscle fiber.
•the plasma membrane of the muscle fiber includes junctional folds
•the neuron releases acetylcholine (inactivated by acetylcholinesterase in the cleft) that binds to ACh receptors
•the motor unit = neuron and the myofiber it loves
The relationship between the motor end plates, t tubules and sarcoplasmic reticulum
Intrafusal Fibers
In order to accomplish smooth movements, the brain needs to know about the tension in a muscle and the load it is supporting.
Extrafusal and Intrafusal fibers:
1. Muscle Spindles:
i. Red lines are motor innervation (contract, shorten)
ii. Blue lines are primary sensory innervation
Nuclear chain fibers- bottom black fiber
Nuclear bag fibers is the top white fiber
When the muscle stretches, the sensory tells the brain that they are, then motor neurons sends the message from the brain back to the fiber to reflex properly
Cells bodies in dorsal root ganglia sensory neurons – always pseudounipolar neurons
It’s all about length
2. Golgi Tendon Organ
Muscle Biopsy 1
Muscle biopsies from 2 different patients, both with complaints of chronic muscle weakness reveals the images shown below
A: many WBCs between the fibers – muscle infection; myocitis
B: many WBCs that are destroying the fibers – autoimmune; myasthenia gravis
Muscle Biopsy 2
Muscle biopsies from a 29-year-old female with progressive weakness of 2 months duration reveals the image shown below.
Muscle atrophy (bottom fascicle) due to loss of innervation – shanked or stabbed; when the neuron dies the axon dies and then the muscle atrophies progressively and shrink in size
Muscle Spindle 1
how can you tell: there is a capsule around them; they have actin and myosin so stain dark
The pink moon shaped thing: blood vessel
Muscle Spindle 2
Find the spindle
Golgi Tendon Organ
Golgi tendon organ: sensory axons wrapped around collagen fibers; detect load
When there is a heavy load – negative feedback that inhibit the muscle; the brain is determining that it is too heavy for them and the muscle collapses to prevent tears and injury
Skeletal Muscle Blood Supply
•skeletal muscle receives a rich blood supply
•the capillaries run longitudinal and parallel to the myofibers
•there are numerous cross-connections between blood vessels
Regeneration
Gross damage can be repaired to some degree by fibroblasts. Adult fibers contain satellite cells situated between sarcolemma and the endomysium à serve as a reserve of embryonic myoblasts.
The vessels have been injected with red gelatin
Regeneration: skeletal muscle can regenerate to some degree; limited
Cardiac Muscle
Not as nucleated
Intercalated discs
Branching of muscle fibers
•found in the heart and the base of large veins that enter the heart
•the myofibers are long, branching and formed by individual, mononucleated cells joined in an array
•Intercalated discs – sites of attachment of neighboring cells
•the nuclei are centrally located (located peripherally in skeletal muscle)
•Some atrial fibers contain secretory granules (ANP and BNP)
Intercalated Discs
1.Maculae adherentes/desmosomes - holds the cells together
2.Fasciae adherentes – adherens, transverse component, hold the cells together, thin filaments anchor here
3.Gap junctions – provide ionic continuity between adjacent myocytes, part of the lateral component; allow adjacent cells to communicate and ions to flow between them
Electomicrograph
Red line: intercalated discs – not really straight; 3 different functions
Only in cardiac muscle – if one fiber is excited the other fibers must as well; it is a massive network; work as a unit whereas the skeletal muscles don’t always have to be this way
Mitochondria – black things at the bottom
SER and Transverse Tubules: Cardiac Muscle
•the t tubule system is not as well organized as that of skeletal muscle; exists as a unit of membrane per sarcomere
•in cardiac muscle there is only one t tubule per sarcomere
•The DIAD: t-tubule + cisterna of sarcoplasmic reticulum
Cardiac Muscle Contraction and Repair
Contraction
•all cardiac myofibers have a spontaneous beat
•in the heart, this beat is initiated by specialized, modified myofibers that are organized into bundles (e.g. Purkinje fibers)
•the heart muscle is innervated by the autonomic nervous system
Repair:
•mature cardiac muscle fibers do not divide and so there is very little capacity for repair
•dead cells are replaced by scar tissue
Smooth Muscle
•found lining the GI, UG and respiratory tracts, blood vessels, iris and ciliary body of the eye, dartos muscle and erector pili
•occurs as sheets of fusiform cells (20 to 200 microns in length)
•nuclei are located in the center of the cell and usually have a “corkscrew” appearance
•smooth muscle cells are surrounded by basal lamina, secreted by the smooth muscle cells; also secrete ECM (collagen, laminin, elastin); some have endocrine function (juxtaglomerular cells – renin)
Fusiform looking cells
Not fibers or branching cells
Smooth Muscle: Z disc
•in the EM cytoplasmic densities can be observed - these densities contain aggregations of actinin à”Z disc”
•intermediate filaments and actinin function like the Z disc in skeletal muscle
•smooth muscle cells are capable of undergoing mitosis (uterus)
Wall of an organ – so smooth muscle somewhere
DICT
Collagen is eosinophilic so stains pink and typically squiggly when it surrounds smooth muscle (green arrow)
Darker purple – bundles of smooth muscle (red)
Smooth Muscle Contraction
Actin and myosin are linked to the dense bodies and to the plasma membrane
•contraction is initiated by a rise in cytosolic Ca++
•Ca++ causes myosin light chain kinase to phosphorylate myosin à can then interact with actin (dephosphorylation stops contraction)
•full contraction can take up to 1 sec
•contractions are slower, can last much longer and are more energy efficient
Smooth muscle contains no t tubule system and the SER sequesters Ca++; gap junctions connect smooth muscle cells.
Contraction
•long, sustained contractions
•peristaltic contractions
•under the control of the ANS
•hormonal control – control by the endocrine system
•nerve terminals are small (compared to the motor end plate)
You can see the squiggly nuclei during contraction
