Mm Histology 4 Muscle

Front 1

Four types of contractile (muscle) cells

Back 1

Skeletal

Smooth

Cardiac

(Also: Myoepithelial Cells - cells that secretes stuff, like milk)

Front 2

Skeletal Muscle

Back 2

The type of muscle that powers movement of the skeleton, as inwalking and lifting

AKA "striated muscle"

The majority of muscle tissue in the body

Under control of the somatic (voluntary) nervous system

Connected at either end to bone

Front 3

Macro structure of skeletal muscle:

Tendon

Fascia

Epimysium

Fascicle

Perimysium

Muscle fiber (aka myofiber)

Endomysium

Back 3

Tendon - attaches muscle to bone, made of collagen.

Fascia - outermost connective tissue that separates muscles from each other

Epimysium - connective tissue sheath that surrounds the muscle (under the fascia). It inserts into the tendon.

Fascicle - a bundle of muscle fibers grouped into a compartment

Perimysium - layer of connective tissue that surrounds each fascicle

Muscle Fiber (aka myofiber) - individual muscle cell within a fascicle. They extend from tendon to tendon.

Endomysium - connective tissue that surrounds each small muscle fiber. "loose aerolar connective tissue"

Front 4

Structure of each individual muscle cell (aka muscle fiber) :

Myofibrils

Myofilaments

Sarcomere

Back 4

Long string with multiple nuclei on the outside of the fiber

Myofibrils - Long strands of proteins (the actin and myosin)

Myofilaments - one strand of myofibril

Sarcomere - one segment of a myofilament. Extends from Z line to Z line

Front 5

Sarcomere structure

Z line (aka Z disk)

M band (aka M line)

Thick Filaments

Thin Filaments

H band

I band

A band

Back 5

Z line (aka Z disk) - dark line at the end part, separates each sarcomere

M band (aka M line) - center line of the sarcomere, doesn't move

Thick Filaments = Myosin

lie at the center of the sarcomere and overlap the thin filaments

Thin Filaments = Actin

attached at one end to a Z disc and extend toward the center of the sarcomere

H band - Part of the thick filament that is not currently overlapped (middle part of the sarcomere)

I band - Part of the thin filament that is not currently overlapped (extends across the Z line)

A band - The length of a thick filament

NOTE - the H & I bands change length, the A band does not.

Front 6

Role of Nebulin, Alpha actinic, CapZ, and Tropomodulin in thin filaments

Type of myosin in thick filaments

Role of Titan in thick filaments

Back 6

Nebulin - controls the length of the thin filament.

Alpha Actinin / CapZ - insert + ends of actin into Z disks

Tropomodulin - inserts the - end into M line

These all cap actin so it doesn't dissociate and remains stable in muscles

Myosin II - dimer of 2-heavy chains and 4-light chains.

Titan - anchors myosin into the Z discs so that they retain alignment relative to actin.

Front 7

Muscle contraction

Tropomyosin

Troponin (I, C, T)

Back 7

In muscle contraction, myosin heads in thick filaments bind to G actin in thin filaments. This pulls them toward the middle of the sarcomere.

Actin (thick filament) first needs to be "uncovered"

Tropomyosin - long protein that runs along the grooves of actin

covers it and prevents myosin from attaching

Troponin - small protein attached to tropomyopsin

if Ca attaches to troponin, tropomyosin cover is released and myosin can now attach to actin and contraction can occur

Troponin I - binds to actin and inhibits actin’s interaction with myosin

Troponin T - binds to tropomyosin.

Troponin C - minds to Ca swivels the complex, and tropomyosin changes its position in the actin groove to open the myosin binding site on actin.

This allows these filaments to crossbridge with the myosin motor head.

Front 8

Cross Bridge Cycle

Back 8

Myosin heads can bind specific sites on actin, forming "cross-bridges" between the 2 filaments.

Cross-bridge cycle:

1. ATP binds to Myosin Head, myosin is release from Actin

2. ATPase in Myosin Head splits ATP to ADP + Pi, Myosin Head cocks back to the next level of Actin

3. Pi is released and Myosin head binds to this next level of Actin, wacking it forward like a hammer. This is the POWER STROKE.

4. ADP is released and now Myosin head is back attached to Actin.

Each myosin filament has many myosin heads and the contraction of the sarcomere involves many cycles of interaction between actin and myosin.

Front 9

Innervation of skeletal muscle

T-tubule

Sarcoplasmic reticulum

Back 9

An action potential is sent from a motor neuron to the muscle

T-tubule - small tube that runs across the muscle fiber from the membrane to the sarcoplasmic reticulum (it is an extension of the plasma membrane)

Depolarization sweeps down the t-tubule from the plasma membranes into the sarcoplasmic reticulum

Sarcoplasmic Reticulum - smooth ER found in muscle cells that surrounds myofibrils.

The only difference between this and smooth ER in other cells is the proteins bound to their membranes and within the lumen

The sarcoplasmic reticulum stores and releases Ca ions when signaled, while the normal ER synthesizes molecules

This Ca attaches to troponin and initiates the cross-bride cycle

The sarcoplasmic reticulum also has active transport Ca ATPase proteins (called SERCA) in the membrane to take up Ca from the cytosol after it has been released

Front 10

Ryanodine receptors

L-type channels

Back 10

Ryanodine receptors - proteins in the SR membrane. Activated ryanodine receptors release a lot of Ca from sarcoplasmic reticulum.

Ryanodine receptors are activated by both mechanical and Ca mediated changes (the mechanical coupling is more important to activate it)

L-type channel ( aka the DHP receptor) - voltage sensitive protein in the T tubule that releases Ca when depolarized

This forces conformational changes in ryanodine receptors that sit across in the neighboring sarcoplasmic reticulum.

Front 11

Rigor Mortis

Tetanus

Back 11

Rigor Mortis - the stiffening of muscles soon after death because of NO ATP

Tetanus - continuous high frequency stimulation of the the muscle results in continuous cross bridges and high degree of force generation.

Front 12

Skeletal Muscle Growth/Repair

Myoblast (aka sarcoblast)

Slow muscle fibers

Fast muscle fibers

Satellite cells

Myostatin

Back 12

Myoblast (aka sarcoblast) - an undifferentiated cell that becomes a muscle cell

During development, myoblasts fuse and become multinucleate tubes.

Differentiation of muscle fiber types then depends on innervation.

Slow muscle = red muscle

contains a lot of myoglobin and NADH

For sustained contraction (ex. antigravity muscles)

Fast muscle = white muscle, "fast twitch"

Contains a lot of glycogen for anaerobic metabolism via glycolysis, but less myoglobin

Can fatigue quickly.

A muscle fiber can contain both slow and fast contraction units.

Postnatal growth - adding fibrils and/or fusion of satellite cells under weight training/exercise. There is no division of cells postnatally.

Myostatin - a protein growth factor that inhibits the growth of muscles and prevents them from growing too large. Begins working in early embryonic development and continues throughout life.The knock out creates the “mighty mouse”.

Repair of torn muscle is mostly due to scarring, which is a process of sealing using connective tissues.

This intercalates (inserts within) in the midst of the muscle cells (aka repair is not the result of new growing muscle cells).

Satellite cells - stems cell that lies next to a skeletal muscle fiber. Plays a role in muscle growth, repair, and regeneration.

Stem cells, which can add to muscle, is really a small component of repair.

Front 13

Smooth Muscle

Back 13

No troponin, tropomyosin or organized sarcoplasmic reticulum

Single nucleus per cell, in the middle.

Force starts intrinsically

Front 14

Multi unit vs. Unitary Smooth Muscle

Back 14

Multiunit There is 1:1 coupling of nerve and smooth muscle cells for temporally precise and organized contraction, ie there is multiunit innervation by a nerve (vas deferens and only a few other sites--some blood vessels).

Unitary - Most smooth muscle is “Unitary” due to gap junctions and fewer innervations are needed (i.e. bladder, stomach). This allows slow, widespread contraction.

Front 15

Contraction of smooth muscle

Caveolae

Back 15

Caveolae - small pockets at the cell surface similar to T-tubules. This is where depolarization occurs (from the neuron).

Contraction in a smooth-muscle cell involves the forming of crossbridges and thin filaments sliding past thick filaments. Shortening occurs in all directions, causing cell to twist.

Depolarization/repolarization involves opening and closing of Ca and K channels at different speeds

Calcium ions regulate contraction in smooth muscle, but they do it in a slightly different way than in skeletal muscle.

Front 16

Cardiac Muscle

Back 16

Created for prolonged contractions

Nuclei are in the middle, single nucleus per cell

The are attached attached end to end to each other and are much shorter than skeletal muscle cells. They branch to form irregular patterns and form short sheets, with important connective tissue elements between the branches

Force starts intrinsically

Front 17

Intercalated discs

Macula adherens

Gap Junctions

SA nodes

Back 17

Intercalated discs - junctions between cells where force is delivered. It is a fascia adherens like site (like zonula adherens-disc).

Macula adherens (desmosomes) - anchor intermediate filaments in the same orientation as the fascia adherens

Gap junctions - allow cells to contract simultaneously. Lined up side by side.

SA nodes - pace the heart

Front 18

Orientation of cellular connections

Back 18

Gap junctions are perpendicular to the myofibrils (lateral face)

Fascia adherens and desmosomes mostly parallel (transverse face) to myofibrils, but sometimes parallel

Front 19

T tubules in cardiac muscle vs. skeletal muscle

Excitation-contraction coupling (L-type Ca channels)

Back 19

T tubules are present at Z discs

1 per sarcomere.

Excitation-contraction-coupling is dependent on L-type Ca channels to trigger Ca influx

(whereas in skeletal muscle the L-channel is coupled mechanically to ryanodine receptors and the Ca influx is less important)

The Ca influx induces Ca release from the sarcoplasmic reticulum inducing contraction.

T tubules are bigger than those of skeletal muscle and bring L-type Ca2+ channels deep into cells. Ca2+ entering from the L-type channel promotes Ca2+-induced Ca2+ release from the SR via Ca2+ release channels (ryanodine receptors).”

Hence while this process is similar to skeletal muscle there is a more important focus in cardiac muscle on Ca conductance via L-channels in T-tubules (aka the initial trigger)

Front 20

Myoepithelial cells

Back 20

Epithelial cells that are hormonal regulation for contraction

(ex. oxytocin for secretion of milk from breast)

Not linearly organized (branched), or created for force multiplier