Intro slide of Ch.

6
- major organs: bones, cartilage (cartilage that is found on the articulating surfaces of the
bones); ligaments that attach bone to bone, tendons that attach muscle to bone; inside the
bone is bone marrow
Functions: structural support (supports entire body) and protection for other tissues (i.e.
cranial bones protecting the brain, pelvic girdle protecting the urogenital organs,
hypofissial fossa protects the pitutary gland which is also called the hypofisis?); stores
calcium and other minerals, major inorganic component of bone is hydroxyapatite; we
put calcium to makes it hard and also helps increases blood calcium; forms blood cells,
hematopoiesis occurs in the bone marrow of the bone; leverage

Slide 6-1
- bone shapes: flat bone (parietal, occipital bones), sutural bones (found in sutures); long
bone (humerus, femur, radius, ulna, tibia); irregular bone (vertebra- singular, vertebrae-
plural; sphenoid, ethmoid); sesamoid bone (develops in the tendon, example- knee cap or
patella); short bone (carpal and tarsal bones)
Long bones develop from cartilage; flat bones develop in mesenchyme

Slide 6-2
2 different forms of bone (also called osseuous tissue) tissues: compact bone or dense
bone- very solid tissue, found on outer surface of bones; found on outer surface of the
humerus or femur or outside bone collar of diaphysis is the compact bone; smallest
structural and functional unit of bones- osteons; osteons are also called haversian
systems; there is a central canal or haversian canal is right in the center of an osteon
where you can find blood vessels and lymphatic vessels; bone matrix is avascular so you
get nutrition from the central canal; you can diffuse through cartilage matrix but you
cannot diffuse through bone matrix; the osteocytes are radiating around the central canal
bc those canals are what is keeping them alive and where they get nutrients from (in the
blood vessels). The blood vessels transports the nutrients to the lacunae through tunnels
called canaliculi. Haversian system can only get so big bc the cells around it are
dependant on nutrition from it and diffusion is distance limited.

Slide 6-3
- spongy bone (cancellous): meshwork of osseous spicules called trabeculae; found in the
interior of the long bone; found in the ephiysis of long bone; you will always find bone
marrow there; red bone marrow: always doing hematopoieisis; yellow bone marrow: fat;
as you get older the red bone marrow is going to become fat or yellow marrow
There are a lot of spaces devoid of bone. There is still hydroxyapaptite and collagen.
There are no osteons or haversian systems.
No spongy bone where there is a lot of stress applied. It is a strong bone but not as strong
as compact bone

Slide 6-4
In the bone collar of the diaphysis, you find compact bone. In the ephiysis you will find
the spongy bone; in the spongy bone spaces you will find the bone marrow; articulating
cartilage is a hyaline cartilage and is found on the surface of the ephysis; inside of the
diaphysis is the arrow (medullary cavity) but when you get older it is all fat inside of
there; we use the fat for stored energy; right now in the ephysis of our long bones you are
actively making blood cells in your bones; most active site of red blood cell formation:
cranial bones
Inside surface facing your brain- compact bone; outside surface is compact bone; right
between the two is spongy bone
Periosteum- allows bone to grow apositionally or interstitionally
Ephyseal line: cartiliage is found here; bc it is in a adult bone, the cartilage is gone and
now we just have lines; in a child it would be called a ephiyseal or growth plate but it
wouldnt be a line but just a plate of hyaline cartilage
Nutrient foramen: hole in bone; how blood vessels get into bone and keep the bone alive
and supply the bone marrow
Endosteum- internal lining of the cavity; not in cartilage

Slide 6-5
Flat bone: such as the cranial bone; has two series of compact bone; Inside facing your
brain and outside facing the scalp; spongy bone (diploe) that is sandwiched btwn two
compact bones in the cranium; lining the outside surface = periosteum; lining the inside =
endosteum;

Slide 6-6
- you dont have a lot of cells; you have more EM
- 4 major characteristics:
~ matrix is densely packed with calcified protein fibers (type 1 collagen)
~ matrix contains osteocytes in lacunae
~ osteocytes communicate through canaliculi (little tunnels in bone)
~ periosteum surrounds outer surfaces of bone; endosteum surrounds the inner
surfaces of bone; endosteum lines medulary cavities and lines inner surface of trachilulea
Matrix of the bone: calcium phosphate and calcium hydroxide crystallize to form
hydroxyapatite; calcium and phosphorous = 2 important minerals in the bone; salt crystal
is in its crystal form called hydroxyapatite
- 2/3 of the bone weight is hydroxyapatite which is a salt crystal and makes bone very
hard, but by itself it is very brittle
- 1/3 of the bone is type 1 collagen fibers (organic component); type 1 collagen has a very
strong tensile strength and is a very strong fiber, but by itself you can bend it
- together, the bone becomes very hard but it is not brittle, it is also pliable but not too
pliable

Slide 6-7
- there are 4 types of cells present in bone:
- osteoprogenitor makes osteoblast which makes an osteocyte (forms when an osteoblast
traps itself in a matrix)
-osteoprogeniotor cell came from the mesenchymal stem cell
- osteoclast came from hematopoietic stem cell; osteoclasts are macrophages in your
bone; osteoclasts are a fusion of many monocytes; osteoclasts eat hydroxyapaptite and
type 1 collagen
Slide 6-8
- osteoprogenitor cells come from mesenchymal stem cells; mitotically divide and
differentiate into the only cells they can become called osteoblasts; you can find
osteoblasts in the inner cell layer of the periosteum and in the endosteum
- periosteum has an outer fibrous layer (dense irregular fibrous; fibroblasts and blood
vessels) and inner cell layer (has cells, mesenchymal and osteoprotegenital and
osteoblasts and osteoclasts)
- endosteum is not found in cartilage; is a single lining of cells; identical to the inner cell
layer of the periosteum (has the same 4 cells); is find lining the surface of spongy bone
(trabeculae), lining the haversian canal, lining the inside of a bone collar
- haversian canals run which way? Volkmanns canal run which way?
- endosteum is not an epithelium so it is not a complete layer of cells but you still find
those 4 cells
- why do you find endosteum there? Bc you have mesenchymal stem cells that want to
make osteoprogenitor cells that want to make osteoblasts that want to make bone. you
add bone to the surface of pieces of bone to make it keep growing. Cells in the endosteum
forming bone on the surface of trabeculae

Slide 6-9
- osteoblasts: derived from osteoprogenitor cells; synthesize and secrete the organic
components (type 1 collagen) of the bone matrix; found on the surface of bone meaning
the endosteum; surronded by osteoid; first thing that an osteoblast makes is type 1
collagen; type 1 collagen is the osteoid; eventually the bone will fuse it with
hydroxyapatite and it will be bone matrix proper
- the osteoblasts are making more bone on the surface
- there are osteoclasts that are degrading the bone on the surface
- osteoblasts have receptors for PTH (perrythyroid hormone) that comes from 3 glands
that are posteriorly to the thyroid gland called the parathyroid gland; they secrete the
hormone when there are too low circulating calcium in your blood; if Ca is too low then
blood goes through your parathyroid gland and those cells that secrete PTH sense low
blood Ca and secrete out PTH (an endocrine hormone); PTH will go through your blood
to your bone and it will bind to osteoblasts so that it can get osteoblasts to secrete another
hormone; PTH bound to active osteoblasts actually decreases Ca levels; when an
osteoblast makes bone, it needs two things: it needs ions to make salt crystal
hydroxyapatite and it needs building blocks of type 1 collagen
- collagen is a protein so its building blocks are amino acids; osteoblast takes amino acids
from your blood and takes Ca and P from your blood to make bone; when osteoclast is
degrading your bone, it is actually spitting that stuff back into your blood; if you activate
osteoblast, you decrease the Ca levels. But when you bind parythroid gland to osteoblast,
it tells the osteoblast to secrete a hormone to decrease the activity of osteoclasts which is
good bc osteoclasts will degrade bone and it will spit the Ca into the blood and raise the
Ca levels
PTH tells the osteoblast to secrete a hormone called OSF Osteoclast stimulating factor;
function- degrades bone; generates calcium and blood calcium levels go up

Slide 6-10
- osteocytes: inactive osteoblasts meaning that they are not dead but that they are not
making bone matrix anymore; they are trapped in spaces void of matrix called lacunae;
they have long dendritic processes that run through tunnels of the bone called canaliculi
(a little tunnel in bone ); the osteocytes processes touch each other to form gap junctions
so that they can communicate with each other; canaliculi is a tunnel in the bone in which
you find cytoplasmic processes of osteocytes
- bone matrix is avascular, but to run nutrients through the bone you need to run it
through the canaliculi; in the central canal there are nutrients bc there are blood vessels
- fluid located on the outside of an osteocyte but in the inside of the canaliculi =
interstitial fluid

Slide 6-11
- osteoclasts: giant, motile, multinucleated cells; are actual macrophages; they are
derivatives of monocytes; many monocytes came together to form osteoclasts; they
degrade bone which is also called resorbtion; when they take a chunk out of bone leave a
depression behind when degrade a part of bone called howships lacunae
- inorganic matrix is degraded by acid; osteoclasts run the bicarbonate reaction to
generate protons to erode the acid; also secretes an enzyme called collagenase to degrade
collagen; osteoclasts spits out collagenase and acid on the surface and that is how it eats
bone; it eats up bone extracellularly
- osteoclasts have receptors for calcitonin, Calcitonin comes out of the thyroid gland;
calcitonin decreases amount of calcium; it is opposite of PTH; it directly binds to
osteoclasts and stops them from resorbing bone; if blood ca levels are too high then how
does shutting down osteoclasts make blood Ca levels lower? Directly it doesnt. when
you shut down an osteoclast there is a cell in the back that is always running all day long
called an osteoblast. The osteoblast is actively making bone and osteoclast is actively
degrading the bone. If you shut down an osteoclast then the osteoblast is actively working
which is taking Ca out of the blood to make bone. You make bone stronger when you
apply force to bone. When you apply force to the bone, it grows in that direction but only
when an osteoclast degrades it somewhere and an osteoblast makes it in that direction.
You increase density of the bone by applying force to it.

Slide 6-12
- it is a battle of the bone bc it is an osteoblast vs an osteoclast; battle goes on throughout
your life; osteoblast is winning in your life; osteoblast is making more bone than the
osteoclasts and that is why your skeleton is intact and your bone has a very high density;
as you get older osteoblasts job goes down bc its hormonal stimulation is going down
(males- testosterone, females- estrogen); since the osteoblasts job goes down then the
osteoclasts job goes higher and it degrades the bone more; this is osteoporisis, everyone
faces this bc osteoblast activity goes down while osteoclast activity goes up, we are
degrading bone more than making it; for women, it is stronger bc after menopause the
estrogen levels drop down to almost zero. Since they have almost no estrogen floating
around then they are not stimulating any sort of osteoblast activity.
- is it good to take Ca supplement when you are older? Yes it is good to take Ca
supplement. Hormonal replacement treatment can always help too
- the osteoclasts have degraded bone and the osteoblasts have regenerated bone; and then
they fill the lacunae with osteoid and calcify the osteoid to make osteocyte in a lacunae;
the lining of cells is called endosteum

Slide 6-13
- compact bone- located where bones are heavily stressed; osteons are lined up in a
unidirectional way and in the bone collar they are lined up as the length of the osteon; the
haversian canals are running the length of the diaphysis
- the osteons are running the length of the diaphysis. Smallest structural and functional
unit of bone = osteon; Center of osteon central canal or a haversian canal; dots radiating
around the haversian canal- osteocytes in the lacunae

Slide 6-14
- haversian canal is lined by endosteum
-trabeculae is lined by endosteum
- question on exam: you walk on the surface of the bone and you fall in, and you need
to know how to get back to the surface of the canal through the volkmanns canal and
haversians canal
- bone matrix is made 4 different ways:
- making an osteon- the matrix is made in concentred rings called concentric lamella;
interstitial lamella (remnants of degraded osteons). The osteoclasts and osteoblasts
remade the interstitial lamellae. The osteoclasts came from the central haversian canal bc
there is endosteum lining it and in the endosteum there are 4 types of cells, one being the
osteoclast. Interstitial lamellae tais holding the two osteons together
- lamellae on the outer bone that is running the whole diameter of the diaphysis/ or outer
circumfrence of the diaphysis is called outer circumfrential lamellae, it is not made of
osteons just bone matrix
- inner medulary cavity has an inner circumfrential lamella
Osteon only has 7 rings of concentric lamella bc diffusion is distance limited; every cell
is depended on the central canal then you cannot have rings that are too far from the
central canal bc they wont get the nutrients
- running in the center of haversian canals are blood vessels; they are connected vertically
to volkmanns canals
- outside of the bone = periosteum, inside of bone = endosteum; periosteum has inner cell
layer and outer fibrous layer; to attach periosteum to the outer circumfrential lamellae:
you take collagen fibers from the outer fibrous layers and you pierce them right in. these
are called sharpes fibers
Bone matrix is avascular; spaces around bone matrix do have blood vessels
Volkmanns canal opens up to a nutrient foramen

Slide 6-15
- spongy bone- located where bones are not heavily stressed; still very hard material and
can withstand stress from multiple directions; like a dense irregular collagenous
connective tissue; fibers are running in every direction; one of the functions is to
withstand stress from multiple direction and to reduce weight of bone ; the skeleton of a
bird is a lot of spongy bone; you can house bone marrow
Head of ephysis is all spongy bone; Spongy bone is made up type 1 collagen and
hydroxyapatite (same materials as compact bone so it is just as strong but since there are
so many spaces it cannot withstand so much stress as osteons can)
- there is still canaliculi bc the matrix is still avascular; there is no haversian canal in the
center, the only thing in the center is another osteocyte in a lacunae; outside is
endosteum;
- in an osteon you have a canal that is feeding the cells peripherally, but in spongy bone
the canaliculi is bringing in blood towards the cell
You find osteoblasts, osteoclasts, mesenchymal stem cells and osteoprogenitor cells

Slide 6-16
- red bone marrow- hematopoiesis and yellow bone marrow is used for fat storage that
could be used for fuel
Bone marrow is loaded with adipocytes, even red bone marrow has a lot of adipocytes.
As you get older you accumulate more adipocytes in the bone marrow and red bone
marrow eventually becomes yellow bone marrow. In your cranial bones, you are making
red blood cells. Specifically in diploe (spongy bone of the cranial bones). Sternum,
scapula, pelvic bone- performing hematopoiesis. Ephysis of long bones do hematopoiesis

Slide 6-17
- fibers coming out from the outer fibrous layer of the periosteum and are going into the
outer circumfrential lamellae- sharpeys fibers or peripherating fibers
- periosteum: outer fibrous layer (dense irregular connective tissue, fibroblasts that made
the connective tissue, and blood vessels) and inner cellular layer ( mesenchymal stem
cells, osteoblasts, osteoclasts, osteoprogenitor cells)
- endosteum is the same as the inner cell layer of the periosteum

Slide 6-18
Bone develops two different ways embryonicaly: intramembranously and endochondrally
Intramembranously- within a membrane; within mesenchyme; bone starts from scratch;
flat bones and cranial bones develop this way
Endochondrally- within a cartilage; most common; starts from cartilage and then
becomes bone; long bones
Intramembranous ossification: occurs within mesenchyme or a fibrous tissue (in the
dermis of the skin, you can make dermal bones); most flat bones like cranial/skull bones
develop this way
Steps in intramembranous bone formation:
~ mesenchymal cells differentiate into osteoprogrenitor cells and then into osteoblasts;
osteoblasts makes collagen called osteoid; ossification center is established; bony
spicules are formed (trabeculae)
~ vasculature becomes trapped within trabeculae; bone marrow sets up here
~ bone remodeling leads to osteon formation, you can remodel spongy bone (trabeculae)
and make it into compact bone; peripheral- if you have spongy bone to the outside and
fusing all the spongy bone together to make compact bone; add peripheral mesenchyme
forms periosteum and endosteum
Slide 6-19
- chunk of spongy bone, connect pieces of spongy bone together; and you fill in a bunch
of gaps and you form outer circumfrential lamellae; you just turned the outside of the
spongy bone into compact bone; this is how you make cranial bones: you fuse all of the
outside and inside spongy bone together to make compact bone. That is why the outside
and inside is both spongy bone and between the two is spongy bone. We cant take
compact bone and turn it into spongy bone.
-The bone is being made right in mesenchyme. The mesenchymal stem cell decided it
wanted to become osteoprogenitor cells and then that made osteoblasts which then made
bone. Then the bone put themselves in places devoid of matrix called lacunae. On the
outside of trabeculae is endosteum. Theres a specifity to which way the bony spicules are
facing. The head of the femur is getting hit from every direction from the acidobolum so
it is lining the trabeculae in every direction in which the forces are applied. If your pelvic
bone shifts one way and you get force applied that way then your femur will grow in that
direction.
- this is the cancellous region (spongy bone area) where you find blood vessels and
eventually bone marrow.

Slide 6-20
- endochondral ossification: requires a hyaline cartilage template; most long and short
bones develop this way
- Primary Ossification Center Events:
- hyaline cartilage model of the bone is developed; the cartilage will grow interstitionally
and apositionally
- chondrogenic cells of the inner cell layer of the perichondrium differentiate into
osteoprogenitor cells that give rise to osteoblasts (at this point you just converted your
perichondrium into your periosteum); occurs at midriff of the diaphysis of the cartilage
template
- osteoblasts form bone right below the periosteum called the subperiosteal bone collar
(IM ossification); the bone is made from scratch so it is intermembrane ossification
- cartilage is avascular but has a perichondrium that diffuses nutrients into it to keep it
alive; bone collar (nothing can get through) cuts off nutrient supply to core chondrocytes
so then the cartilage cells are dying; osteoclasts cut a hole into the bone collar and the
periosteum grows into the diaphysis; when periosteum comes in that means that
osteoprogenitor cells and osteoblasts and osteoclasts are all coming in.
- osteoclasts make way for a periosteal bud (osteoprogenitor cells, hematopoietic cells to
make bone marrow, blood vessels to get around haversian canals)
- once inside the midriff of the diaphysis of the cartilage template, osteoprogenitor cells
give rise to osteoblasts, the osteoblasts are laying bones right on top of the cartilage; you
initially make an ocified bone matrix ontop of a calcified bone matrix, you eventually
dissolve the cartilage away and are left with bone, osteoblasts are going both ways
replacing cartilage with bone
- osteoclasts carve out marrow cavity to lighten up the bone; osteoblasts are still
migrating bone collar lengthens but cartilage is still diving interstitionally; in your life
you have osteoblasts chasing chondroblasts both ways, until age 18-20 the chondroblasts
are dividing faster than the osteoblasts and you continue to grow; since cartilage still
keeps growing your bone is actually growing bc the bone ends up replacing the cartilage;
bone grows in length by cartilage growing in length. Around age 18-20, osteoblast
activity is more than chondroblast activity then the osteoblasts will completely replace
the cartilage. When you replace the growth plate cartilage then you can never grow
in length again.
Why females are generally shorter than males: Estrogen has greater effect on osteoblast
activity than testosterone. Estrogen stimulates osteoblasts to remove cartilage faster so
then your growth plate is being removed faster therefore females dont grow as tall

Slide 6-21
- cartilage template completely hyaline cartilage; pericondrium surrounds the cartilage;
pericondrium is diffusing nutrients into the cartiliage matrix to keep it alive; something
stimulates your pericondrium to become periosteum; the inside layer of your periosteum
that has osteoblasts is going to end up making bone; you start forming a collar of bone
that eventually becomes the diaphysis of your femur; when you make bone you cant
diffuse nutrients into the cartilage anymore; the cartilage cells die, an osteoclast will cut a
hole into the collar and things will just cruise into the bone; when an osteoclast cuts a
hole then your whole periosteum invades into your cartilage and the osteoblast label the
cartilage and the cartilage will be dissolved and you will end up with bone. The
osteoblasts keep growing in that direction towards each epiphysis and they are replacing
cartilage as they go. They get up to a certain region and they slow down. This region is
called the growth plate (all hyaline cartilage) and doesnt get replaced until age 20. this is
how you grow in length. They dont replace the cartilage on the surface of the bone called
articulating cartilage. Articulating cartilage is a shock absorber between your bones and is
never replaced. So as the bone grows towards the ends of the epiphysis , the osteoclasts
eat away at the center of the diaphysis forming the medulary cavity. All of these events
occur at the primary ossification center.
The primary ossification center is the center of the diaphysis which is also called the
midriff of the diaphysis of a cartilage template.

Slide 6-22
Secondary ossification center: bone invades the ephysises
Basically it is the same thing but you just dont make a bone collar; you have
osteoprogenitor cells invading right into the cartilage matrix and replacing it with bone.
The articular cartilage will never be replaced at the ends of the ephysis, but will
eventually be replaced at the growth plate cartilage

Slide 6-23
- bone grows in length by cartilage growing interstitially; bone cannot grow by itself.
Bone can only grow apositionally
- bone growth begins at 6th week and ends in the 20s; puberty and hormones have effects
on bone growth; bone growing in spurts during puberty is because of GNRH and
testosterone and estrogen levels increasing making osteoblast and chondroblast activity
very high
- someone exercising at a very young age like prepuberty, in a male they are generating
testosterone before it should even be there. If testosterone is there at age 10, it is going to
stimulate osteoblasts to divide greater than chondroblasts and you are going to close your
ephyseal plate earlier than you should and you remove your growth plate at an early age.
You can stunt your growth before puberty.
- there are gender and height difference
Achondroplastic dwarfism- a cartilage disorder, most common type of dwarfism; you are
making cartilage fine but you are not replacing the cartilage with bone very well, there is
a problem with ossification

Slide 6-24
- density or mass of bone is greater in people who are more active; being more active
allows you to flow more interstitial fluid through your canaliculi
- the head of the femur can withstand forces coming from every direction; the forces will
come down through the diaphysis and the osteons are lining down that way of the
diaphysis; the forces go all the way down to the end of the femur and eventually have to
spread out to two bones (tibia and fibula)
- long bone can break when it gets a blow to a horizontal of the diaphysis bc the bone
cannot withstand great force from that direction bc the osteons are not lined up in that
direction

Slide 6-25
- skeleton has a calcium reserve; PTH increases blood calcium levels by stimulating
osteoblasts which stimulate OSF which bind to osteoclasts and increase their activity
calcitonin directly binds to osteoblasts and shuts it down
PTH works in small intestine and increases calcium absorption directly; PTH can also go
to the kidney and stimulate reabsorption of calcium; when PTH goes into small intestine
it works together with calcitriol to faciliate absorption of calcium; calcitriol is a
derivative of vitamin d that you make in your skin
Calcitonin will decrease blood calcium levels, it goes to bone and shuts down osteoblasts;
calcitonin can work in small intestine by decreasing activity of PTH or calcitriol;
calcitonin can go to the kidney and tell it to dump calcium into your urine, while PTH
tells the kidney not to dump the calcium into the urine
If you are not making enough vitamin D bc your skin is not absorbing enough sunlight
then you are not making calcitreol then you are not going to properly absorb calcium in
your small intestine, if you dont then your bone calcium is going to be low then your
bone density is going to be low. If you cant make hydroxyapatite then you cant make one
of the main components of the bone. Hydroxyapatite makes the bone hard so then
without it you are making the bone more pliable. This disease is called rickets in children.
Which is a calcium disorder. They are not getting enough vitamin d or calcitriol. Bones
are very pliable bc they are made of collagen. Brittle bone disease- you are making
hydroxyapatite fine but you cannot make collagen, therefore the bone is very hard that
they are brittle. This disease is also called osteogenesis imperfecto. It is a defect in
collagen composition.

Slide 6-29
- adult form of rickets- osteomalacia
- osteoporosis- loss of bone mass due to increase in osteoclast activity relative to
osteoblast activity

Intro Slide for 10

- major organs: skeletal muscles (muscles that attach to skeleton); there are 2 other types
of muscle in the muscular system: cardiac muscle in your heart and smooth muscle
everywhere in your body; skeletal muscles are attached to your body via fibrous like
structures called tendons; a big flat tendon= aponeuroses (which is like a tendinous
sheet);
Functions: provides movement (force generated by muscle pulls on bone and then bone
acts a lever for that force generated by the muscle); responsible for posture (muscle cells
are constantly contracting in your body tonicaly); provides protection and support for
other tissues (we have a thoracic cage that protects our heart and lungs; what protects our
abdominal organs- skeletal muscle); generates heat that maintains body temp. (reason you
have 37 degree body temperature is because the muscle cells are doing cellular
respiration; a muscle cell doing cellular respiration makes ATP but our muscle cells are
very inefficient at making ATP; so then all that energy that is lost is lost as heat); guards
entrances and exits of our body (we have a tube inside of a tube, big GI tract, at one end
we have the oral cavity and at the other end we have the anal cavity, we have skeletal
muscle guarding both one entrance and one exit; in our lips we have the muscle called
obiqularis oris which is the kissing muscle and that guards the entrance of the oral cavity;
at the other end we have the anal sphincter muscle that guards that exit

Slide 10-1
~ 3 types of muscle tissues:
1. skeletal: striated (we see banded like lines under the microscope); voluntary
(we have to make conscious commands for skeletal muscle to move); attached to the
skeleton
2. cardiac: striated; involuntary (we cannot consciously control cardiac
muscle to contract); heart muscle (we only find it in once place- the heart)
3. smooth: no striations; involuntary; GI tract (found all through the GI tract)
Anatomy of skeletal muscle: associated with connective tissue, nervous tissue and
vasculature; the skeletal muscle intervated? by nerve fibers controlling it, you find
connective tissue holding all of the muscle fibers together, you find vasculature there to
keep alive
~ 3 layers of CT:
- epimysium: outermost connective tissue; dense collagen CT (explains why tendons are
very strong); surrounds muscle organs
- perimysium: connective tissue in the middle; dense collagen / elastic CT; contains
nerves and vasculature; surrounds muscle fascicles which are bundles of muscle cells
- endomysium: innermost connective tissue; loose / reticular CT; contains capillaries
(smaller versions of blood vessels), nerves terminals (smaller versions of nerves) and
stem cells; surrounds muscle fibers
* fuse at the end of a muscle (tendon or a aponeurosis)

Slide 10-2
- they took part of the bicep brachea and pulled it out; they took a cross section of the
bicep and you can call it a skeletal muscle or a muscle organ; you can see the muscle
organ has connective tissue that surrounds it so if you were scraping on your bicep on the
outside then you would be scraping on the epimysium; the big muscle is made up of a
bunch of circular structures. These circular structures are called muscle fascicles; each
muscle fascicle has connective tissue that surrounds it called perimysium; we take the
perimysium and connect it all together and form a epimysium around that and you form a
skeletal muscle or muscle organ; if you look inside the fascicle, there are a bunch of
circles and you pull one of those circles out and you get a muscle cell, we call the muscle
cell a muscle fiber bc they are really long fibrous structures; the muscle cell has
connective tissue that surrounds it and that is called endomysium; so take a muscle cell
and wrap endomysium around it, take a bunch of cells and wrap perimysium around it to
form a fascicle; take a bunch of those fascicles and wrap epimysium around it then you
form a muscle organ
- imagine that all of the white connective tissue is endomysium; all the red is the muscle
fibers and muscle cells; imagine all the white coming out of the screen and the red stuff
staying behind so imagine epimysium, endomysium and perimysium coming out and
when all those tissues come out they form a bundle called a tendon; the connective
tissues work past the organ and form a tendon
- we have an individual skeletal muscle cell which we call a muscle fiber or myofibers
(myo- muscle); the cell needs to have a plasma membrane which is called the
sarcolemma; beneath the plasma membrane should be cytoplasm and there is and it is
called sarcoplasm; the cell is responsible for shortening so then it has proteins that
shorten and those are what the red dots (the cylinders) are called myofibrils; the
myofibrils are found in the cytoplasm of the cell called sarcoplasm; myofiber contain
myofibril
- just parietal to the sarcolemma- endomysium; visceral to sarcolemma- sarcoplasm;
whats in the sarcoplasm is the myofibrils; in the endomysium you find nerve terminals,
capillaries, and stem cells (called satellite cells that are cells that looks like its orbiting
around another cell); it a stem cell from the skeletal muscle but its activity is pretty much
zero

Slide 10-3
- nucleus of the skeletal muscle cell; there is no room for it in the middle of the cell bc
there are so many myofibrils so that nuclei is pushed off to the periphery; many nuclei in
a skeletal muscle cell; take the skeletal muscle cell and surround it with an endomysium;
bundle a bunch together and surround it with a perimysium and form a muscle fascicle;
take a bunch of fascicles and surround it with epimysium and you form a muscle organ;
the nerve fibers and blood vessels are going down through the perimysium and
endomysium and finally reach a cell and at the cell the blood vessels provide nutrients
and the nerve terminals are synapsing with muscle cells and they are controlling them to
contract
- there are many nuclei bc skeletal muscle is a fusion of many cells; we take myoblasts
(that are stem cells) and fuse them together to form skeletal muscle cells; skeletal muscle
cell is a synctyium (before we were talking about osteoclast; but now we are talking
about a skeletal muscle that is a fusion of many cells, a fusion of many stem cells called
myoblasts); many myoblasts fuse together and keep one common plasma membrane and
all the nuclei and cytoplasm stay within it; some of the myoblasts dont fuse and stay in
the endomysium and they are satellite cells or stem cells; myoblasts come from
mesoderm
- skeletal muscles are called muscle fibers bc they are long, clyindrical, multinucleated
cells bc they are a fusion of cells; it is not uncommon for the muscle cell to be as long as
the organ itself; there are muscle fibers as long as your biceps
- you see vertical lines and these vertical lines are called striations (which are
manifestations of the myofibrils); myofibrils have these light and dark regions to them;
these light and dark regions can be seen under the microscope and we call these striations
- it is 99% sure that the muscle cells cant divide, but some can divide

Slide 10-4
~ The Sarcolemma and Transverse Tubules
- sarcolemma is the plasma membrane of a muscle cell; RMP (-85mV) means that
the cells can be excited and they can be depolarized; if you depolarize these muscle cells,
they will shorten
- sarcoplasm is the cytoplasm; contains myofibrils, mitochondria, glycogen (skeletal
muscle stores a lot of glucose as glycogen) and SR (sarcoplasmic retiuclum which is
modified smooth endoplasmic reticulum, function- stores calcium), sarcoplasmic
reticulum stores calcium in muscle cells; SR is just an organelle derived from the SER
- sarcolemma= t tubules; t-tubules is just a projection of the sarcolemma, t-tubule is
just an invagination of the sarcolemma; T tubules conduct the signal to contract
throughout the entire muscle fiber
~ Myofibrils
- long, cylindrical bundles of myofilaments inside of the sarcoplasm
- two primary components of myofilaments are: primarily actin (thin filaments) and
myosin (thick filaments); when muscle contracts, actin is sliding past myosin; and since it
is a filament sliding past another filament we call it the sliding past theory of muscle
contraction
- myofibrils are repeating units of sarcomeres; when you assemble thin and thick
filaments together you form sarcomeres; sarcomeres are the smallest structural and
functional unit of skeletal muscle; bunch of sarcomeres lined up end to end is called
myofibril; arranged in units called sarcomeres (units of muscle contraction)
~ The Sarcoplasmic Reticulum (SR)
- analogous to SER; it has 2 regions: terminal cisternae and sarcolemma (triad)
- stores calcium; calsequestrin; calcium pumps (ATPases)

Slide 10-5
Sarcolemma of the cell
The plasma membrane dips inward and forms these tubes in your cells; these tubes are
called the t-tubular network; they are just invagination of the sarcolemma; t-tubules are
part of the plasma membrane; plasma membrane dips inside of the cell; if you crawled
inside of that t-tubule, you can crawl outside of another one bc both of them are
interconnected to each other; if you get an action potential on the surface of the cell then
you can get it down in the middle of the cell too; what is happening on the outside of the
cell can happen in the interior of the cell; only happens in the muscle cell; blue = SR;
make the t-tubule instead of yellow, you would make it red bc it is just plasma membrane
- if you were inside of the t-tubule, where would you be? The fluid surrounding you
would be called the interstitial fluid; you can be standing on the T-tubule and still be
standing on the surface of the cell. Standing inside of the T-tubule, you will still be on the
surface of the cell. If you stick your finger in a balloon you will form a t-tubule. Your
finger is not inside of the balloon, it is still on the outside of the balloon
- the t-tubule sends a signal to contract deep down in the cell; the signal to contract is
called the action potential

Slide 10-6
- bunch of mitochondria crammed btwn myofibrils; blue are thick filaments and red are
thin filaments; sarcomere is there; what surrounds every myofibril is an organelle is blue
called SR; SR is a membranous bag, a lipid membrane that has calcium in it; it stores
calcium inside of itself so that you dont store calcium in the sarcoplasm bc if calcium is
in your sarcoplasm then your muscle cell will shorten; if the signal to contract is calcium
and you have a lot of calcium in the sarcoplasm then your muscle cells will be constantly
contracting then they will be constantly shrinking; we store Ca in the sarcoplasmic
reticulum so when we want the muscle cells to shorten we take the calcium from the SR;
when we dont want cells to contract then we suck it back up into the SR;
- the SR is analogous to the smooth endoplasmic reticulum; it has 2 regions to it; it has a
region called terminal cisternae and a region called the longitudinal region which is pretty
thin; at the end of the longitudinal region is a dilated region which is terminal cisternae;
dilated regions of sarcoplasmic reticulum are called terminal cisternae; take 2 terminal
cisternae and sandwich a t-tubule in the middle then you form a triad
- if the signal to contract is on the surface of the plasma membrane, it will travel down
the t-tubules, the plasma membrane gets excited, when the plasma membrane gets
excited, it will rub off that excitement on the sarcoplasmic reticulum, when the
sarcoplasmic reticulum is excited it will spit Calcium out; when Ca is released, it gets
dumped right on the myofibril, calcium allows thin and thick filaments to slide past each
other; there is a protein in the terminal cisternae that stores calcium called calsequestrin;
calsequestrin holds calcium in high concentration; calcium pumps in the longitudinal
regions of the sarcoplasmic reticulum, calcium ATPases, calcium pumps suck calcium
back into the sarcoplasmic reticulum
~ Sarcomeres
- repeating bundles of myofilaments
- smallest structural and functional unit of muscle
- muscle contraction results from the interactions between myofilaments ( the thin and
thick filaments are sliding past one another causing the muscle to shorten; a thin filament
will never interact with a thick filament unless calcium is involved, signal for muscle
contraction is calcium and that is why you want to keep Ca in the SR or thin and thick
will always be passing each other)
- thick filaments, thin filaments, stabilizing proteins (stabilize sarcomere), regulatory
proteins (regulate interaction btwn thin and thick filaments, there is a protein that binds
calcium that allows it to be the regulatory protein that it is)
- give myofibrils/muscle cells a banded appearance (dark A and light I bands)
- light, dark, light, dark regions- that is what you see when you look under a microscope;
the boundaries of one sarcomere are 2 Z lines; a myofibril is a repeating unit of
sarcomeres; what attaches to the Z line are thin filaments, thin filaments horizontally
attach and they run to the M line; the M line is the center of the sarcomere, the M line has
thick filaments running in the opposite direction towards the Z line
- in the center is the M line and attached to the M line are thick filaments; the length of
the thick filaments is called the A band; the length btwn the thin filaments and the center
of the sarcomere is called the H zone; the distance between the thick filaments of one
sarcomere to the thick filaments of an adjacent sarcomere is called the I band; I band is
split over 2 sarcomeres; zone of overlap- zone where thin and thick filaments overlap,
most important zone bc when these 2 interact the sarcomere shortens; thin filaments slide
relative to the thick filaments and the sarcomere shortens

Slide 10-7
- sarcomere is made of thin and thick filaments; thin- actin; thick- myosin; myofibril is a
repeating monomer of sarcomeres; myofibrils are found in the sarcoplasm of myofibers
which are skeletal muscle cells; thin and thick filaments are the main proteins but there
are stabilizing and regulatory proteins; each individual sarcomere has a dark and light
band to it; the light region is the I band and the dark region is the A band; H zone-
distance between thin filaments and the center of the sarcomere; A band- length of thick
filaments; I band- distance between thick filaments on adjacent sarcomeres; zone of
overlap- where you find thin and thick filaments overlap; I band is split over 2 adjacent
sarcomeres; boundary of sarcomeres- z lines; z lines come closer together; I band and h
zone get smaller; zone of overlap gets larger, a band never changes
- you only find thin filaments in an I band making it lighter; you find thin and thick
filaments in A band making it darker so there is more protein picking up more stain
- nuclei is pushed off to periphery
- connective tissue outside of the sarcolemma- endomysium
- fibroblasts are making the connective tissue so they are found in the endomysium

Slide 10-8
- thin filaments are attached to the z disk via filaments called actinin proteins; actinin
proteins attach actin to the z disk; in the z disk, there are green proteins that are
stabilizing proteins that are called titin proteins; I band- we see thin filaments and the
green proteins (titin proteins); we have myosin proteins attached to the M line; h zone-
myosin proteins and the green filaments (titin proteins) are in the center of each myosin
proteins ; titin protein attaches to z disk, runs right through myosin and attaches to the M
line; zone of overlap- titin in the center of myosin, myosin in the center of 6 actin (thin
filaments); imagine the purple proteins (myosin filaments) are staying in place and the
red proteins are being pulled towards you; 2 different ways to look at it: myosin with 6
actin around it or 1 actin with 3 myosin around it; myosin has head groups that grab on to
the thin filaments and pivot them and pull them, that is the sliding filament theory
- this is the resting sarcomere; if it was compressed you would find thin filaments in the I
band; thick filaments would be in the I band if the sarcomere was contracted; H band
would have thin filaments in it if it was a contracted sarcomere;
Slide 10-9
Thin filament attaches to the z line via actinin; coily type proteins attached to the z line
called titin; titin is an elastic protein
Titin prevents sarcomere from overstretching
Thin filaments are made of 4 proteins: the principal protein is actin; major protein is
called F-actin; F-actin is two strings of beads coiled around each other, F stands for
filamentous; each individual actin monomer is called g-actin; G stands for globular; we
assemble all of these small G-actin monomers into two strands of beads called F-actin;
nebulin is a protein in the middle that helps g-actin monomers assemble into f-actin
filaments; two proteins so far- nebulin and f-actin; other 2 are regulatory proteins called
troponin and tropomyosin; tropomyosin covers these yellow sites on g-actin called active
sites; 1 tropomyosin molecule covers about 7 active sites so it covers about 7 g-
monomers; each individual tropomyosin has an individual troponin associated with it;
each g-actin has an active site and the active site is for myosin; the head group on myosin
binds to the active site on g-actin; tropomyosin blocks the active site, when tropomyosin
is removed from the active site then myosin can bind
- thick filament are primarily myosin; the myosin proteins look like golf clubs; the handle
is attahced to the m-line and the club region is pointed towards the z line; there are
several myosin proteins; myosin head group bind to actin monomers; at rest the myosin
head groups are facing the z line; they bind to actin and they pivot the other way then
they are bound to actin, they will bring the whole framework inwards; and that is how the
z line comes closer, the I bands disappear, the sarcomere gets shorter; it looks like titin
attaches to the end of myosin but it actually runs through the whole center

Slide 10-10
- left- relaxed sarcomere; right- contracting sarcomere: I band is shorter; h zone is
shorter; z lines are closer together; a band is never changing
- bottom picture is of an entire myofibril that is relaxed, myofibril is a repeating monomer
of sarcomere;
- bottom is of a myofibril that is contracted; I band is shorter light region; the z lines are
closer together; darker in the center bc the proteins are coming closer to the m line;
overall myofibril is shorter; individual sarcomeres are shortening and entire myofibril is
shortening; now this has to be transduced to the plasma membrane so that the whole
sarcolemma can shorten so when the muscle cell membrane shortens, the whole muscle
fascicle shortens so that when the fascicle shortens then the organ will shorten and when
the organ shortens it will pull on a tendon and then the tendon pulls on a bone and then
something moves
- you can have myofibrils shorten as much as you want but if they are not attached to the
plasma membrane, then the muscle cell doesnt actually shorten then it is all pointless
- actual protein that attaches myofibrils to a plasma membrane is dystrophin; dystrophin
attaches the z line to the plasma membrane of a skeletal muscle cell; muscular dystrophy-
genetic abnormality where they are not making the protein or the protein is dysfunctional,
and the muscle is not contracting properly so they are atrophing which means they are
wasting away

Slide 10-11
Summary diagram- you can see there is an epimysium that surrounds muscle organ, pull
out one circle and you have a fascicle and surrounding that is a perimysium; pull one of
those circles you have a muscle cell and you have endomysium; pull out of one these and
you have a myofibril and you see individual units of sarcomeres; you can see t-tubules,
sarcoplasmic reticulum; longitudinal region; terminal cisternae and calcium pumps, you
have calcequestrin storing a high amount of calcium; when calcium is dumped into the
zone of overlap, than thin filaments can interact with thick filaments; thick filaments cant
generally interact with thin filaments bc tropomyosin is interacting with the active sites
on g-actin; calcium binds to troponin so that troponin can move tropomyosin out of the
way

Slide 10-12
- muscle fibers generate a tension ; the tension is transferred to a tendon; think of tension
as a force; overall movement exists if the tension generated in your muscle fibers is
greater than the resistance that you are applying to the muscle fiber; if you put a weight in
your hand and you cant lift it, you cant lift it bc you are not generating more force than
the resistance; if you generate more force than the muscle will shorten and the weight
will move

Slide 10-13
F The Control of Skeletal Muscle Activity
- contraction results from voluntary commands generated in the CNS; Central nervous
system or also called somatic nervous system controls skeletal muscle cells; two
functional divisions of our nervous system: somatic division and autonomic division;
somatic division only controls skeletal muscles and they are all efferent commands;
autonomic division- is all efferent commands but this controls all things that you cannot
consciously control such as cardiac and smooth muscle meaning your heart and glands
- axons pierce into your muscle and branch in perimysium and end up in your
endomysium and terminate as synaptic terminals or synaptic knobs
- muscle and nerve intercellular connection is a called a synapse, more specifically it
is called a neuromuscular junction; if it was a neuron from your brain connecting with
another neuron, we call that a neuroneuro junction; but this is a neuron fusing with a
skeletal muscle so it is called a neuromuscular junction; connection is in parenthesis bc
the two cells dont actually touch each other bc there is a space between the two that is
called the synaptic cleft
- neuromuscular junction = terminal knob (end of the neuron) + synaptic cleft (a space) +
motor end-plate (cell after the synapse- the muscle cell, the specific region of the muscle
cell is called the motor-end-plate)
- specific region of the sarcolemma of the skeletal muscle cell involved in a synapse is
called the motor end-plate; the specific region of the neuron involved in the synapse is
called the terminal knob; space between the two is called the synapse
- MJ stands for myoneural junction and can be said either way as myoneural or
neuromuscular (NMJ)
- you can see the manifestions of the dark and light filaments through the myofibril; there
should be a space between the sarcolemma and the terminal knob called the synaptic cleft
but you cant see it in the image
- when the sarcolemma gets under the terminal knob, that is called the motor end-plate

Slide 10-14
~ Motor Neurons
- somatic motor neurons control skeletal muscles
- multipolar (efferent) neurons
- cell bodies of the neurons are located in CNS (either from brain or spinal cord); axons
are in PNS, peripheral nervous system, (cranial and spinal nerves); we have skeletal
muscle in our face, in our scalp we are controlling those muscles through the cranial
nerves
- synaptic terminals specifically terminal knobs in muscle, they are in endomysium, they
are synapsing on the skeletal muscle cells
- multipolar neuron looks like: it has dendrites on one side; long slender process called
axon on the other side; axons are found in the nerves that are going out to the skeletal
muscles; the terminal knobs synapsing with your muscle cells; cell body originates in
spinal cord in this example, axon goes out through spinal nerves and spinal nerves
eventually form terminal knobs that will synapse with the skeletal muscle, spinal nerves
exit the spinal column through intevetebral foramens

Slide 10-15
- light micrograph: you can see axon, terminal knob, you can see dark and light bands,
you can see the sarcolemma that goes right below the terminal knob; the arrow pointing
at the knob that they say is the motor end plate isnt actually the motor end plate, it is the
terminal knob, beneath that is the motor end plate of the muscle cell; there are little holes
in the membrane dipping down forming t-tubules

Slide 10-16
You see the terminal knob and the motor end plate; the sarcolemma is now beneath the
terminal knob and it is all folded up; we call these regions that are folded up junctional
folds; the plasma membrane is convoluted beneath the synaptic terminal ; it is convoluted
to increase surface area for a membrane protein, the membrane protein is an acetylcholine
receptor; the acetylcholine receptor binds a neurotransmitter called acetylcholine; you can
have more of these receptors in the membrane if you have more membrane so you
convolute the membrane beneath the synaptic terminal; we call these convolutions
junctional folds and we call that whole region motor end plate; t-tubule and junctional
folds are not similar at all except for that they are invaginations of the sarcolemma
- in these synaptic knobs, we have synaptic vesicles that contain neurotransmitters;
specifically in neuromuscular junction the neurotransmitter is acetylcholine; when the
nerve fires an action potential, the action potential stimulates the vesicles to undergo
exocytosis and they dump the neurotransmitters into the synaptic cleft, the
neurotransmitters diffuse through the space and bind to the receptors and when they bind
to the receptors they will stimulate the muscle to contract

Slide 10-17
- there is a terminal knob, synaptic vessicles
- the synaptic vesicle is undergoing exocytosis bc calcium is coming into the knob;
calcium is coming in through a channel called calcium voltage gated channel; neurons
have a resting membrane potential of -70mv so that means that they can be excited; that
also means that there is more negative inside than on the outside; if you make the neuron
more positive inside than outside then you have depolarized/ excited the neuron; if you
depolarize the terminal knob then you open the calcium voltage gated channels and then
calcium comes in and stimulates the vesicles to undergo exocytosis; action potential is
causing calcium to come into terminal knob and stimulate vesicles to undergo exocytosis;
the vessicles release neurtransmitters into the synaptic cleft; neurotransmitters in the
synaptic cleft will now diffuse over to the post synaptic cell and bind to the receptor; the
cell located before the synapse- presynaptic cell; the cell located after the synapse- post
synaptic cell
- the neurotransmitter acetylcholine and the enzyme acetylcholine esterase that degrades
acetylcholine in the synaptic cleft; if acetylcholine excites muscle cells then it will always
excite muscle cells unless you degrade it; we dont want our muscle cells to always be
excited; to stop the acetylcholine, we tell the neuron to stop releasing acetylcholine but
there is still acetylcholine from the previous stimulus so to get rid of the acetylcholine we
take the acetylcholine esterase and we degrade the acetylcholine
- we call the receptor in the motor end-plate : a nicotinic receptor or a cholinergic
receptor; we call it a cholinergic receptor bc it binds acetylcholine and we call it a
nicotinic receptor bc it binds nicotine
He calls it a ligand gated Na channel, ligand general signaling molecule; gated channel
that allows Na to come into the cell; it looks like a receptor but it is not just a receptor bc
when acetylcholine is released it creates a hole in the membrane to allow sodium to come
in; sodium will come in when the channel is open bc there is more sodium on the outside
and there is more on the outside bc of the NaK pump; acetylcholine receptor is just a
ligand gated channel so that when acetylcholine binds then it will open a channel and lets
sodium come into the post synaptic cell
- the post synaptic cell is a skeletal muscle cell and has an RMP of -85mv that means
when Na comes into the cell, it depolarizes the cell, the sodium makes the cell more
positive; when a cell has a RMP of -85mv and you let NA come into it then you can
reduce that to 0 that means then that the inside and outside have the same amount of the
positive charges then you have no polarity
- When you let sodium come in then you reduce polarity, the reduction in polarity is what
actually excites the cell; so Na causes a reduction in polarity in the post synaptic cell
- if you dont run a NaK pump then you dont have a Na concentration gradient, you can
run the acetylcholine gated channels all you want but if there is no sodium concentration
gradient then there will be no movement of Na then no muscle will contract; such as your
diaphragm wont contract and you wont breath
- things that bind to the acetylcholine gated channel- nicotine, acetylcholine, a toxin
called cuyrary (spelling?), cuyrary is a toxin from plants that binds to the nicotinc
receptor/ ligand gated channel but it doesnt activate it meaning it doesnt open it and let
sodium come into the cell so it competitively inhibits the binding of acetylcholine so
acetylcholine is released but it has nowhere to bind to bc cuyrary has already bound to all
of the receptors, but when cuyrary binds to the receptor it doesnt let sodium come in and
the muscle cell is paralyzed, your neurons are working fine and releasing acetylcholine
- your diaphragm is skeletal muscle so if you have enough toxin then you can stop
breathing and eventually die
- in the presynaptic cell, there is a neurotoxin that causes blockage of transmission called
botulinum toxin; botulinum toxin works on the synaptic knob, when it gets into your
body it diffuses into the interstitial space of your synaptic cleft and it gets taken up to the
synaptic knob; when it gets into your synaptic knob it prevents the formation and release
of acetylcholine. Your neurons work well but they cant release acetylcholine so then they
cant bind to the receptors so then you have paralysis of the muscle
- botulinum toxin does presynaptic blockade and cuyrary mediates post synaptic blockade
- myasthenia garbis- disease where you make an antigen that looks like and acts like
acetylcholine and it binds to the receptors but doesnt allow them to do anything and
eventually causes paralysis

Slide 10-18
- the terminal knob is getting excited; the red line is a wave of depolarization which will
cause calcium to come into the terminal knob; exocytosis of neurotransmitters;
neurotransmitter is released and binds to its receptors on the junctional folds/ ligand gated
sodium channel; sodium comes in and depolarizes the cell; acetylcholine esterase
degrades acetylcholine; the degradation products of acetylcholine are going to be
reabsorbed and put back together so they can be spit back out
- on the right is a neuromuscular junction, there is an action potential going down the
terminal knob; voltage gated calcium channels are opening and they are stimulating
synaptic vessicles to undergo exocytosis; synaptic cleft you have neurotransmitters

Slide 10-21
Neurotransmitter is released binds to the receptors on junctional folds of the motor end
plate; Na comes in; and now the action potential is traveling; at rest you plasma
membrane is more negative inside than it is on the outside, but when you get more
positive inside than the action potential is beginning bc you are depolarizing the cell
The reason you have an invagination of the membrane so that something can travel across
the membrane and not something to travel through the tube. Eventually when you get to
the bottom of the tubule, there is a protein in the membrane that is also voltage gated
called DHP receptor or dihydropyridine receptor. When the action potential gets to DHP,
DHP receptor gets activated and undergoes conformational change. It has a physical link
to a protein in your sarcoplasmic reticulum. The protein in the SR is called the ryanodine
receptor. When you excite the t-tubule protein, the coil will open the ryanodine receptor.
When it opens it, calcium comes out of the Sarcoplasmic reticulum. This region of SR is
called the terminal cisternae and in the terminal cisternae, calcequestrin holds Ca in high
concentrations. Ca is released into the sarcoplasm and binds to troponin and then troponin
pulls tropomyosin away from the active sites so that myosin can bind to actin and when
myosin binds to the active sites, the myosin pivots and pulls the actin towards the m-line.
When myosin pivots, the z line moves and you are dragging the thin filament towards the
m-line

Slide 10-22
Ca is released into the sarcoplasm and binds to troponin and then troponin pulls
tropomyosin away from the active sites so that myosin can bind to actin and when
myosin binds to the active sites, the myosin pivots and pulls the actin towards the m-line.
When myosin pivots, the z line moves and you are dragging the thin filament towards the
m-line.
How do we get calcium back into the SR? through the calcium pumps that are located in
the longitudinal regions of the SR.
If you want to stop a muscle cell from contracting: you have to ultimately stop a neuron
from releasing acetylcholine, allow acetylcholine esterase to degrade acetylcholine and
remove from receptor, close the receptor so you dont let anymore sodium come in,
repolarize the cell by letting sodium flow out through K leak channels, repolarizing
membrane then the DHP wont be excited anymore and then he is not pulling the gate
open anymore and then we can suck calcium back into the SR through calcium pumps.
We suck calcium back through the pumps then it will let go of troponin and then troponin
lets go of tropomyosin and tropomyosin covers the active sites and myosin cant bind so
then the muscle cant contract.
Important step in relaxing a muscle is sucking up the calcium back into the SR.

Slide 10-23
- this shows an action potential going down the t-tubule allowing the sarcoplasm to
release calcium specifically in the zone of overlap region. This is the best region bc the
thick filaments are overlapping the thin filaments.

Slide 10-25
Cross bridge cycling is when the myosin head groups pivot; the myosin head group binds
to acin, they will pivot and break away and then pivot and do it all over again; this is
called cross bridge cycling
At rest the myosin head groups are point towards the z line. They are pointing toward z
line and at rest the myosin head group has 2 things attached to it: ADP and inorganic
phosphate. They are not technically relaxed bc they have adp and Pi attached to it. ADP
has hydrolyzed itself so that energy is released so the myosin head group is energized and
is waiting to bind to actin to drive actin towards the m-line. Tropomyosin is blocking the
active sites, but when you put calcium in the mix, calcium will bind to troponin and it
will pull the tropomyosin away from the active sites and now myosin can bind to actin.
When it binds to actin, the protein will undergo conformational change and it will spit out
ADP and Pi. ADP and P actually fall off and that stimulates the myosin head group to
pivot and drags actin towards the mline.
To keep cross bridge cylcing going is to break the cross bridges so that the myosin head
groups can keep attaching. To do this: you bring ATP in and it breaks the cross bridges.
When atp binds to the head groups, it breaks the cross bridges and the head group is still
pivoted towards the mline. A relaxed myosin head group has ADP and P bound to it and
binds to actin and loses the ADP and P and then it pivots. ATP binds to it then it just drops
off. When atp hydrolyzes into ADP and P it will cause the myosin head group to cock
back and face back towards the z line.
When you think of muscle force, it is a myosin head group binding to actin and acting on
it. The myosin head group pivots because it is bound to ADP and Pi.
Rigor mortis- a situation in which you cant break myosin cross bridges, you cant break
myosin cross bridges bc you cant make ATP bc you are dead and you are not doing
cellular respiration. These people are considered stiff bc their head groups are stuck to the
actin and they cant make ATP so then their cross bridges cant break. It loosens up after a
while bc the enzymes in the lysosomes are released and start dissolving the proteins away
and the cross bridges break apart.

Slide 10-28
- summary of everything we talked about

Slide 10-29
F Tension Production by Muscle Fibers:
- sarcomeres shorten which will cause a myofibril to shorten; fiber shortens, organ
shortens
- amount of tension produced depends on cross-bridge numbers; the more myosin you
can bind to actin the greater tension/ force you can generate; you can form more cross
bridges if you have an ideal sarcomere resting length meaning do you have an optimal
zone of overlap before you began to contract bc if you do then you will get more cross
bridges then more tension; and to get more cross bridges you can increase frequency of
stimulation of neurons, if you fire the neuron more frequently then you will release more
calcium into calcium and you will cause more myosin-actin cross bridge
- if you are studying a muscle of a person who has been working out for 6 months, they
stimulated more actin and myosin in the muscle. For people who do resistance training,
they gain more force because they are generating more actin and myosin for cross
bridges. These people make more than those who dont exercise bc they have more
myosin and actin. People who exercise are getting more muscle, they are just making
their muscles bigger to store more myosin and actin to make more cross bridges.
Two things that can increase formation of sarcomeres: Optimal resting length of
sarcomere and increase of frequency of stimulation
Anaerobic steroids can enhance this. A person who looks really huge one day and then 3
months later he looks really small. The main reason is because they have gained a lot of
water in their cells and the water is eventually going to go away after they stop using the
steroids. Steroids stimulate your body to increase protein synthesis: make more myosin
and actin, increase mitochondria to store more glycogen
- tension production in muscle fibers is an all-or-none principle meaning when you
stimulate a neuron to contract a muscle it will either contract or not, the muscle fiber is
either on or off
~ Length-Tension Relationships:
- sarcomere has an optimal working range; maximum amount of cross-bridges are
formed and maximum tension is produced
- compressed (shortened) and stretched (overlengthened) sarcomeres cannot produce
maximal tension
- arrangement of muscle, CT and how they are attached to our bone prevents extreme
compression or excessive stretching
The normal arrangement of our skeleton according to our skeletal muscle and the
connective tissue (i.e. tendons) prevents muscles from over compressing or over
stretching. Another thing that prevents muscles from over stretching are stretch receptors
in our muscles. There are stretch receptors in your muscle that sense the force and
generate force that is much stronger than that. The stretch receptors, bone and the
connective tissue associated with the bone prevent them from being overcompressed or
over stretched. Think of the bicep muscle. You can flex it as much as you want but you
cant flex past a certain point

Slide 10-30
This shows tension produced in a muscle.
On the x-axis It shows the sarcomere length. this shows tension at its maximum at the
peak and its tension at its lowest on both sides. You see the sarcomere at its optimal
resting length meaning a good degree of zone of overlap, the maximum amount of cross
bridges can form here, and a lot of actin and myosin binding here. On the left side the
muscle is overcompressed and the tension generated is reduced. On the right side the
sarcomeres are overstretched and the zone of overlaps are shrinking. Then you are
forming less cross bridges so then less tension.
In one of the pictures you say that the zone of overlap is greater than in the other so there
should be more tension, but the problem is that the thin filaments keep stretching over
each other in the sarcomere. The thin filaments go to each of the z-lines and they start
interacting with each other negatively such that it inhibits cross bridge formation.
If you have a sarcomere too compressed then you have your myosin proteins stuffed into
your zdisk. Even though you have a huge degree of overlap, the sarcomere cant go
anywhere and it is overcompressed.

Slide 10-31
~ The Frequency of Stimulation
- single stimulation produces a single contraction (muscle twitch); a twitch is much
different than what cause useful work in our body; useful work in our body is generated
by sustained muscle contraction
- twitches vs. sustained muscular contractions or a tetanus (which causes constant
contraction): twitch stimulates a muscle to contract but than instantly relaxes, you cant
move with a twitch
How do you go from a twitch to a sustained muscular contraction? Add a bunch of
twitches together. Increase stimulation frequency.

F Twitch Contractions
- single stimulus-contraction-relaxation sequence is a twitch in a muscle fiber
- myogram is a graphical representation of this sequence of events
- on the right is a myogram of a twitch contraction, time is in msec so very fast, at time 0
that is where you applied the stimulus to the muscle cell, the stimulus is acetylcholine
binding to muscle cell. The nerve fires at time 0 and at 2.5 msec nothing happens.
Nothing meaning no contraction. At point 2.5msec then you get tension rising and it hits
a maximum and it starts dropping off.
-there are 3 periods of a twitch contraction: the first one is called a latent period,
contraction phase, and relaxation phase.
- in a myogram, you can talk about a lot of things happening with the skeletal muscle just
by looking at the curve. Between time 0 to 2.5, no tension is being generate. Nerve is
releasing acetylcholine by exocytosis bc calcium came into the synaptic knob.
Acetylcholine binding to the ligand gated sodium channels. Sodium comes in and causes
local depolarization of the motor end plate. Sodium diffusing to the periphary opening the
voltage gated sodium channels at -60mv. The voltage gated sodium channels open all the
way down the t-tubules and activate the DHP receptor which then activates the gate of
DRY receptor on the SR and then calcium comes out and binds to troponin. This is all
still in latent period where this is no tension. Calcium binds to troponin and then troponin
binds to tropomyosin and then myosin can bind to actin. This is still all latent period.
What is the beginning of the contraction phase? You see first tension when the myosin
head groups pivot. You first see tension when the myosin head groups lose ADP and
inorganic phosphate and actually pivot. Then you see a bunch of pivoting and cross
bridge cycling. Then you hit a maximum tension and then things start dropping off.
Things start dropping off bc the tension frequency is 1. it will begin to relax bc
acetylcholine is going to be degraded by acetylcholine esterase and then removed from
the receptor. Receptor closes and K leak channels are leaking K so that the membrane
potential can go back to normal (-85). DHP will let go of DRY and DRY will close. Ca
pumps will suck Ca back into the sarcoplasmic reticulum and the muscle cells will relax.
That is only one twitch.
You dont move with a twitch. But if you add a bunch of twitches together then you will
get a sustained contraction which is normal movement in our body.

Slide 10-32
F Treppe- happens when you add a bunch of twitches together
- if a muscle cell is stimulated immediately after the end of the relaxation phase of a
previous stimulus (10-20/sec) (basically it is saying that if you stimulate a muscle cell
and you relax it and then you hit it again with a stimulus), the contraction that ensues will
develop a slightly higher maximum tension than the previous one (if you do a twitch
contraction, you will get x tension; if you stimulate the muscle right after the twitch is
gone, you will get a little more tension. Tension starts building up after you add more
twitches together); You need to get 10-20 action potentials per second to get the treppe
phenomenon. Treppe means stairs so it is a like stepwise buildup of tension. increase
continues over first 30-50 stimulation
- that line shows the maximum tension you can get in a muscle . In treppe, you are only
getting of that. You stimulate the muscle, it relaxes and then you stimulate it again
immediately after and hit it with a little more tension. After 30-50 stimulations, it just
plateaus off.
- this is called the warm up phenomenon. You are getting this build up of tension by
adding these twitches together over time is because the muscle is actually getting heated
over time. People take advantage of this while they work out. They lift light weights for a
while before lifting heavy weights. What they are doing is they are letting their muscles
go through these twitches and adding a bunch together and letting their muscles go
through treppe. You are heating up your muscles. Heated up muscles have their
sarcoplasmic reticulum release calcium more efficiently. More calcium that is released
then the more calcium binds to troponin which then the more troponin binds to
tropomyosin which then allows more myosin to bind to actin. If you bind more myosin to
actin then more cross bridges form and more tension is formed. Cold muscles dont
contract as well. Warm muscles contract better bc the enzymes are working better and the
reactions are going faster. Ca flows out better when the muscle cell is warmed up.
- tension rises in steps called treppe; further tension produced remains constant; warm-
up phenomenon
- why does it plateau? Bc of your stimulation frequency is too broad. It is 10-20/sec. it is
too broad. If you increase stimulation frequency then you can build up more tension

Slide 10-33
F Wave Summation and Incomplete Tetanus
- what explains a incomplete tetanus is a wave summation. Your stimulation frequency is
greater here. It is 20-40/sec and not 10-20/sec.
- if a second stimulus arrives before the relaxation phase has ended from the previous
stimulus, the relaxation phase cant end bc the stimulus frequency is greater, you are not
letting your muscle cell relaxes before you hit it again, (20-40/sec) a second, more
powerful contraction occurs
- stimulus frequency; twitch, treppe or wave summation? Increased stimulus frequency,
you move from treppe into wave summation; wave summation explains what you get
with a typical muscle contraction called the tetanus; this is an incomplete tetanus
It is called incomplete bc your wave frequency is not at maximum. You still have a
situation where the tension drops, but nonetheless you still have a sustained muscle
contraction.
The question is hwy? you have increased your muscle frequency, why is it now that the
muscle cell is generating more tension? It is bc calcium is stuck in the sarcoplasmic
reticulum. You stimulated the muscle cell to contract and before it completely relaxes,
you didnt suck out all of the calcium so there is still some calcium left over. So then you
hit it again and you add more calcium to already preexisting calclium and you can form
more cross bridges, it hits a maximum but the maximum is the maximum force that the
muscle fiber already had.
One of the main reasons for wave summation: left over calcium in the sarcoplasm
between muscle contraction will give rise to wave summation
Complete tetanus on the right and incomplete tetanus is on the left- the only difference is
the stimulation frequency is so great that the relaxation phase is gone. You dont have
these valleys but just a fused line of tetanus where the stimulation frequency is so great at
40-50/sec.
- a muscle producing peak tension during rapid cycles of contraction and relaxation is in
incomplete (unfused) tetanus

Slide 10-34
One of the main reasons for wave summation: left over calcium in the sarcoplasm
between muscle contraction will give rise to wave summation
F Complete Tetanus
- muscle is stimulated so frequently that relaxation phase is eliminated (40-50/sec); a
complete (fused) tetanus is short-lived
- relaxation cannot occur since there in not time for Ca2+ reuptake
Complete tetanus on the right and incomplete tetanus is on the left- the only difference is
the stimulation frequency is so great that the relaxation phase is gone. You dont have
these valleys but just a fused line of tetanus where the stimulation frequency is so great at
40-50/sec.
Our muscles generally work through tetanus, incomplete and complete tetanus. They
cycle between these two.

Slide 10-35
F Tension Production by Skeletal Muscles
- amount of tension produced in a muscle organ is determined by: internal / external
tension and total number of muscle fibers stimulated
- total number of muscle fibers stimulated is equal to amount of tension produced in a
muscle organ; what is the maximum tension you can get out of your biceps? You can
contract every muscle fiber in that organ but we dont normally do this. We have motor
units. We have neurons that stimulate just a group of cells in the biceps and another motor
unit that stimulates another group. We dont stimulate them all together at once unless we
were at maximal activity. If we put a maximal load on our arms then we are stimulating
all of our muscle fibers in your bicep. If you turn on all of your muscle fibers in your
bicep then you will reach maximum tension in your bicep.
-two types of tensions: internal and external; internal- tension generated by myofibrils or
sarcomere tension, tension inside of the muscle cell which is essentially the cross
bridging cycle. We are inside of a muscle cell, sarcomere and myofibrils are shortening,
how is it now that the bicep is shortening and tendon is shortening and pulling on bone?
Myofibrils are shortening and they somehow need to be attached to the plasma membrane
through dystrophan. The plasma membrane then shortens. All of the plasma membranes
are connected to each other through a bundle of connective tissue that bundles all of the
plasma membranes in the fascicle. What is the connective tissue? What happens is a
muscle fiber shortens and it stretches epimysium, perimysium and endomysium. We
know that all of these extend past the muscle and form tendons. The force you generated
inside of the muscle has to pull on the tendon and that is external tension. The tendon will
then pull on the bone.

~ Internal and External Tension

- internal tension results from myofibril contraction
- external tension is the tension within the extracellular fibers (endomysium, epimysium,
and perimysium)
- stretched fibers transfer tension to the resistance meaning when you pull on tendon, it
will pull on bone; you have excess tension left over during muscle contraction which can
cause wave summation in a tetanus; in an incomplete tetanus, you stimulate a muscle cell
to contract before it completely relaxes. Muscle cell contracts and puts tension in the
tendon but you dont let the muscle cell completely relax therefore the tendon still has
some tension left in it and then you contract the muscle cell again so you add tension to
the preexisting tension in the tendon. So residual calcium left over from muscle
contraction and residual tension left over in the tendon between muscle contraction are
responsible for tetanus.
- internal vs. external tension; parallel and series elastic elements