A.

Blood
1. Components:
a. Plasma – fluid in your blood; mostly water
b. Cells
1. Erythrocytes - RBCs
2. Leukocytes - WBCs
3. Cell fragments:
a. Platelets (pieces of cells)
b. Megakaryocytes (giant cells that platelets are
made from)
c. Hematocrit
a. Looking for what percent is blood plasma and
what is RBCs
b. Males habe more RBC’s because of testosterone
which stimulates RBC production

B. Plasma Components
a. Most of the plasma is made of proteins
b. There are lots of proteins in the blood, but they don’t get out
because they are too big
2. Plasma proteins
a. Albumins – made by liver and added to blood; largest amount
1. Carriers (steroid hormones)
2. Important in maintaining osmotic pressure of blood
b. Globulins
1. Immunity – antibodies
c. Fibrinogen – essential for blood clotting
1. Interferes with some lab tests
3. Serum – when remove fibrinogen from plasma
4. Bilirubin – what gives plasma its color; a breakdown product of Hb
(Hb=hemogolbin)
a. Should be clear or slightly yellow
5. What other solutes are in plasma?
a. Ions
b. Organic molecules: such as?
1. Sugar
2. Amino acids
3. Vitamins
4. Gases – oxygen, CO2
5. Hormones
6. Metabolic waste products

C. Erythrocytes
1. Major function is to carry oxygen from lungs to the cells & carries CO2
back to lungs
2. It is very flexible because it doesn’t have organelles or nucleus so it
can fold to fit into capillaries
3. Hemoglobin
a. Heme (iron) – can bind oxygen
b. Globin – 4 units; protein portion with one molecule of heme in
the middle of each unit
c. Binds CO2 and CO
d. Can bind to 4 oxygens
4. Erythropoiesis – process of making new RBCs

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 a. Erythropotein is a hormone produced in the kidneys that
stimulates erythropoiesis
b. Occurs in red bone marrow
c. Red bone marrow located in: Spine, ribs, pelvis, and ends of
long bones
5. Reticulocyte – last stage in maturation of erythrocyte; all that is left is
some Rough ER (looks like a spider web)
a. Indicates bone marrow is producing abnormally large amount of
RBCs
6. Turnover (spleen)
a. 1% of RBC’s are destroyed in the spleen and liver everyday
b. RBCs have no nucleus
c. How does that affect them? Only live 120 days (because no
nucleus can’t repair itself)
d. Heme  bilirubin  bile (recycling)
7. Iron
8. Iron deficiency
a. Ferritin – protein that iron binds to when stored in liver
b. Transferrin – protein that iron binds to when carried in blood
c. Iron is recycled – loose some iron everyday
1. From urine, feces, sweat
a. Replace by ingesting food
9. Causes of Anemia:
a. Folic Acid and Vitamin B12
1. Necessary for cell Division
2. Folic Acid is found in green vegetables; necessary for
making new DNA
3. Vitamin B12 is a cofactor, works along with enzyme to
make a reaction go forward
b. Regulations of Erythrocyte Production
1. Controlled by Erythropoietin (kidney)

D. Anemia
1. Decrease in the ability of blood to carry oxygen; due to:
a. Decreased total number of erythrocytes (RBCs)
b. Diminished concentration of hemoglobin per erythrocyte
c. Combination of both
2. Sickle-cell anemia
1. Only one amino acid different in genes that make the
globin that causes the different in shape
b. Sickle-shaped RBC when oxygen is low
1. Results in destruction of RBCs
c. Relation to malaria – helps because the parasites don’t like
sickle-cell

E. Leukocytes – WBCs
1. Classes: basophils, neutrophils, eosinophils monocytes and
lymphocytes
a. Classified according to their affinity for various dyes
b. Granulocytes- basophils, neutrophils, eosinophils: all have polka
dot appearance when stained
c. Monocytes and lymphocytes- are smooth

F. Regulation of Blood Cell Production

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 1. Pluripotent stem cells
a. These cells make either type of blood cell- red or white
b. Happens in the bone marrow
2. Hematopoietic growth factors (HGFs)
a. This is the growth factor that controls what type of blood cells
b. Erythropoietin- stimulates production of red blood cells
c. Colony-stimulating factors (CSFs)- white blood cell production
1. More than one type of colony stimulating factor
2. Lymphocytes are controled more by what you have been
exposed to – inflammation etc.
3. Granulocytes and monocytes
d. Interleukins- white blood cell production
1. Can stimulate production of any type of white blood cell
imaginable
2. Some interleukins are not involved in inflammation
3. Released in blood and will send out a chemoattractin to
get cetain white blood cells to travel to an area
4. Responsible for plaques in blood
5. Mediate inflammatory response

G. Skeletal Muscles
1. Anatomy review
a. Sarco = muscle
1. Muscle fiber= I muscle cell
2. Muscle is a group of cells bound together by connective
tissue
b. Sarcolemma:
1. Name given to cell membrane of muscle cell
c. Sarcoplasm:
1. Cytoplasm of muscle cell- packed with contractile
filaments
d. Sarcoplasmic reticulum:
1. Endoplasmic Reticulum that has a slightly different
structure than that found in other cells- storage place for
Calcium
e. Terminal cisternae:
1. Portion of the sarcoplasmic reticulum that is in contact
with the transverse tubules (like in between the
sarcoplasmic reticulum and transverse tubules)- this is
known as a TRIAD (2 Terminal cisternae +Transverse
Tubule)
f. Transverse tubules
2. Myofibrils
1. Actual part of the muscle that contracts- position of
protiens changes cause a contraction
b. Contractile structures
1. Two types of filaments that make up myofibrils
c. Thick filaments:
a. Basically put about 250 myosin filaments
b. There is an orientation- tails toward center
2. Myosin- composed of four different protein chains-
different kind of myosin for skeletal muscle versus
cardiac muscle

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 3. Tail - heavy chain- two coiled chains of amino acids
wound together
4. 2 heads (constitute the crossbridges)- two light chaings
that make the head- have an Actin Binding site and a
Mysoin ATPase site (enzymatic action)- release energy
when ATP is broken down while attached to Mysoin
ATPase site- when attached to actin called crossbridge
d. Thin filaments:
1. Actin- Two forms- monomer- G-actin (Globular)- when
linked together they are F-actin (Filamentous)
2. Globular (G-actin) proteins polymerized into a chain (F-
actin)
3. Troponin- Protein that are equally spaced along the thin
filament- Three types of protien that make up troponin-
Troponin I -Troponin T- and Troponin C- calcium binds to
Troponin C
a. Active site is where mysoin binds
b. Active sites are covered by tropomysoin when the
muscle is relaxed- if tropomyosin is not covered
than the Actin binding site will immediately bind
c. Ca++ comes in and binds to Troponin C- makes
tropomysoin move which will reveal the active
site
4. Tropomyosin- protein that is found in long chain it wraps
itself around the actin that is all twisted together
3. Ultrastructure
a. Z-disk (or line)- where the thin filaments are anchored start and
end of sarcomere- ZigZag structure made of other proteins
which basically attaches thin filaments together
b. I-band- light part of the Sarcomere- across Z disk- from end of
one A band to start of another
c. A-band-length of thick filament- sarcomere looks dark- Zone of
overlap is where myosin and actin overlaps- there is a precise
arrangement of thin and thick filaments in myofibril- different
muscles have different numbers and different arrangements of
thin and thick filaments
d. H-zone- center of the A band- only has myosin or thick filaments
in it
e. M-line- another protein that makes a line in H zone that
attaches thick filaments to eath other
4. Titin and nebulin- Two proteins
a. Titin: is biggest protein we have found- not only is largest but is
very elastic- attaches the myosin to the Z line- extends from M
line to Z line- attaches all along the thick filament- when muscle
is stretched the titin will help muscle to bring it back to resting
length- overstretch muscle- will pull muscle back to resting
length
b. Nebulin- another very large protein- very inelastic- like a rod-
extends length of thin filament
5. Sliding filament theory of contraction- still considered a theory- cannot
put a live muscle in electron microscope- cannot see I band H band
and A band doing what they do in real time- therefore cannot say this
is 100% accurate we know this is what they do

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 a. A band does not shorten during contraction- not shortened
during contraction- 1954 electron microscope
b. I band and H-zone shorten during contraction- shorten
c. Sarcomere shortens during contraction
d. When muscle is relaxed there isn’t so much overlap during rest-
A band is the same length- in contracted muscle the H band is
very narrrow and can dissappear completely- I band is much
shorter- the sliding filament is the only way this can be
explained

H. Neuromuscular Junction
a. Motor neuron- occurs in center of muscle fiber (motor unit to
muscle)- usually tons of muscle fibers per motor unit
b. Action potential propogated down the motor neuron and three
Action potentials stimulate the muscle fiber- cause release of
Acetyl choline- sarcolemma is an excitable tissue- means that
an action potential can be generated in the sarcolemma
(membrane)- muscle contracts- action potential goes away in all
directions away from the neuromuscular junction
c. The transverse tubules bring action potentials into the interior
of the skeletal muscle fibers, so that the wave of depolarization
passes close to the sarcoplasmic reticulum, stimulating the
release of calcium ions
d. The extensive meshwork of sarcoplasmic reticulum assures that
when it releases calcium ions they can readily diffuse to all the
troponin sites
e. Release calcium at each place where there is a T-tubule

I. Excitation-contraction Coupling
1. Starts with the Action potential reaching the nueromuscular juntion
ending with the contraction of the muscle; these events are coupled
2. Sequence of events
a. Production of end-plate potential
1. One Action potential to generate a contraction- twitch
(action potential)- not the 30 that were needed in motor
neurons
2. Occurs at nueromuscular juntion- Calcium comes into
axon terminal
3. A.P. Along axon --> end bulb
4. Acetylcholine released
5. Binds to receptor on motor end plate- acteyl choline
receptors are here- these are associated with ion
channels- Sodium and Potassium channels will BOTH
open when acetyl choline binds to receptors- net result
of this is lot more positive ions coming into cell than
leaving the cell ending with the depolarization
6. Ion channels in motor end plate open
7. Depolarization- sodium influx and potassium influx
greatly exceeds postassium eflux (from concentration
gradient)- no voltage gated sodium channels in motor
endplate- so when the motor end plate a graded
potential is all that is made- can’t make an action
potential without a voltage gated channel- charge will
open voltage gated sodium channels

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 b. Muscle A.P. Triggered
c. A.P. Moves along sarcolemma and into t-tubules- continues into
muscle fiber
d. A.P. Triggers indirectly causes release of Ca2+ from SR- A.P.
going down t-tubule are not what call SR to release calcium
1. Voltage-sensitive dihydropyridine receptor proteins on t-
tubule- DHP- voltage sensitive gate- in physical contact
with sodium??? it will change shape and open calcium
2. When calcium is released it will bind to troponin C
moving tropomyosin and actin and myosin will bind
together

J. Production of the power stroke

1. Ca2+ binds to troponin- out of SR- (toponin bound to tropomysoin)-
Toponin is like Calcium binding to Calmodulin- Troponin changes shape
2. Tropomyosin moves- uncovers Active site
3. Myosin head attaches- mysoin is kept in state of readiness even in
relaxation (in skeletal muscle)- mysoin head swivels – when myosin
swivels that is a power stroke
4. Thin filaments slide past each other- Z line come towards each other
a. When myosin attached to actin= crossbridges
5. Repeats cycle- 1 A.P. causes MANY power strokes
a. Rigor State
1. Myosin tightly bound to actin there is no ATP or anything
else bound to the binding sites
a. 45 degrees
6. ATP binds to myosin cross-bridge, causing actin-myosin link to break
a. ATP now binds to nucleotide binding site allowing the actin and
mysoin attachment to break atp to ADP and P
7. Myosin cross-bridge swivels back into original position
a. Back to 90 degress
8. Energized myosin cross-bridge combines with binding site on adjacent
actin molecule
9. Energy is released again, causing myosin to swivel back again

a. Energy is released when inorganic phosphate is released- this is

where we have the power stroke (step # 5) exercise
physioology pictures swicel head bacj ti 45 degrees for the
power stroke Actin moves in very small increments with each
crossbridge cycle
b. Not all myosin attach and detach at the same time
10. ATP
11. Myosin head (cross-bridge) swivels towards the center of the
sarcomere
12. 1 power stroke of a cross-bridge results in a small movement of the
thin filament
a. lots of crossbridge cycles for muscle to relax and contract
b. Crossbridge swivels toward middle of the sarcomere each
power stroke moves the filment only a very small distance
13. Each action potential produces many cycles of movement
during a single twitch contraction
Rigor state is when the myosin Is at a 45 degree angle – mysoin is

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attached to G actin without ATP- ATP is needed for the power stroke
Muscles are never at rest in the rigor state
If at rest stiff muscles-
ATP is split into ADP and Pi bur they both remain attached which
energizes the myosin head- it swivels to 90 degrees which is a perfect
position to bind to its actin monomer
Next inorganic phosphate is released
Myosin swings back to a 45 degree angle- pull actin toward middle of
the sarcomere at the end of the power stroke the ATP comes off and at
the beginning – T tubel get action potential into interior of muscle
K. Termination of the cycle
1. Ca2+ ATPases pump calcium back into the SR
a. To allow muscle to relax is that we have pumps that pump
calcium- they are working all the time- calcium released is
pumped back in- Sometimes the pumps are going to fast and
can’t keep up
b. Always pumping calcium back into Sarcoplasmic reticulum
c. As start to pump calcium back it will come of troponin and go
back into SR which will swivel tropomyosin back to cover actin
binding site
d. A muscle at rest is step 4, but it is Ready to swivel
e. Topomysoin controls power stroke cycle from continuing

L. Skeletal Muscle Energy Metabolism

1. 3 ways for a muscle to form ATP:
a. We need ATP to break Rigor state
b. Can’t pump Calcium back into SR without ATP
c. Sodium and potassium ATPase pumps at the neuromuscular
junction The 8 twitches
d. Phosphorylation of ADP by creatine phosphate (happens first,
used quickly)
1. Creatine phosphate is where phosphate comes from to
regenerate ATP- Creatine phosphate
e. Oxidative phosphorylation of ADP, in the mitochondria
f. Substrate level phosphorylation of ADP by the glycolytic
pathway in the cytosol
1. During glycolysis- anaerobic process
g. Muscle glycogen->blood glucose->fatty acids
1. Big store of glycogen- use muscle glycogen stores fairly
early in exercise before start using blood glucose-
gluconeogensis or beta osidation- can’t back ATP fast
enough through beta oxidation fast enough in high
intensisty
h. Glycolysis important at high intensity
1. Becomes anaerobic
2. Oxygen debt- oxygen stores in the muscle- myoglobin

M. Muscle Fatigue
1. Decline in muscle tension as a result of previous contractile activity
a. The amount of tension that develops decreases when you are in
fatigue

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 b. Some muscle fatigue a whole lot and other fatigue slowly-
others fatigue rapidly
2. Rate of recovery- duration & intensity of exercise

N. Reasons for Fatigue

1. Reduction of ATP- not a major contributor
a. Even when a muscle totally fatigued there is still an amount of
ATP
b. Depletion of ATP is not a big contributor to muscle fatigue
2. Depletion of glycogen stores (may affect SR Ca release)
a. Most effect on Sarcoplasmic reticulum
3. Increased H+ and pi interfere with crossbridge cycling
a. Increase of inorganic phosphates is a reason for fatigue- it can
interfere with in organic phosphate and interfere with
crossbridge moving- a physical problem- can change pH of the
muscle which can cause fatigue (lactic acid from hydrogen ions)
4. Calcium channels, Ca-ATPase pumps, troponin, tropomyosin

O. 3 Basic types of skeletal muscle fibers

1. Slow oxidative fibers (Type I, Slow Twitch, and Fatigue -resistant fibers)
2. Fast oxidative fibers (Type II A, Fast-twitch A, and fatigue-resistant
fibers)
3. Fast Glycolytic Fibers (Type II B, Fast Twitch B, or Fatigable Fibers)
a. Muscles contain all three types in differing proportions.
1. Motor unit- 1 motor neuron and all the muscle fibers it
ennervates- A motor unit will only have one type of
muscle fiber- never all three or even two for one motor
unit
b. Order of recruitment- (increase in # of motor units used in a
particular activtiy)
1. Slow-oxidative
a. Have a smaller motor neuron that will fire first
2. Fast oxidative
a. Then these
3. Fast-glycolytic
a. Lastly these- high intensity exercise
c. Muscle
1. Slow oxidative vs. Fast oxidative
a. Has to do with contraction velocity- if slow twitch
fiber x axis and y axis- tension vs. time-
difference is how fast the muscle is able to
shorten and relax
b. Comes from the muscles perferred source of ATP
not exclusively can use other ways to make ATP
but most often used oxidative phosphorylation
c. Have lots lots of myoglobin and mitochondria-
they will be redder than the FG
2. Fast glycolytic fibers-
a. First to fatigue
b. Ton of glycogen- use glycolysis- white meat is the
fast glycolytic fibersmuscle contracts fast but
relaxes quickly too
c. Fast twitch fibers is able to pump calcium back
quicker

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 3. Speed of contraction and Fatigueability
a. FG>FO>SO
P. Mechanics of single-fiber contraction
1. Tension vs. Load
a. Tension is the force exerted on the object by a muscle
b. Force exerted on the muscle by the object
2. Types of contraction
a. Isometric- muscle does not shorten
1. Length of muscle doesn’t change
2. Load is greater than or equal to tansion developed
a. Ex. push the blakc board
b. Isotonic- muscle does shorten-
1. still have to attach dross bridges- but when the cross
bridges swivel get shortening- this is directly related to
how much tension is developed- crossbridges is directly
related to how big a muscle
c. Lengthening contraction-
a. An eccentric contration- have to be careful with
concentric
2. Passive process

Q. Myograms
1. Latent period- before tension
a. Tension in mg – dependent on a value of how many cross
bridges are attached
b. Isotonic contractions graph by how much the fibers have
shortened- how much crossbridge cycling you have- doesn’t
shorten immediately because crossbridges have to bind before
you can get shortening- graphing tension woud look similar to
isometric- can’t shorten in mg
c. Cause- Ca release and binding to troponin
d. Latent period is there while everything takes place
2. Contraction period
a. Depends on time that cytosolic Ca is elevated
b. Time when mucle develop tension until peak tension is reached
1. Depends on which type fiber you are- the reaction time
difference is 10 fold
c. The faster calcium is pumped back into the SR the contraction
stops
3. Relaxation period- due to Ca uptake into SR

R. Frequency- Tension relation

1. Action potentials in a muscle fiber increases the mechanical response
(tension or shortening) up to the level of maximal tetanic tension
a. Max and Min then increase frequency (for summation)- a twitch
usually lasts about 100 miliseconds- as frequency of Action
Potentials increased level of tension increases (mechanical
summation)
1. An increase from mechanical summation can be 3-5
times higher than the single twitch
2. Good way for muscles to increase amound of tension
without increasing work

S. Mechanical Summation

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 1. Tetanus- (look at picture)
a. Incomplete (unfused) - partial relaxation between contractions-
this is phsyiologically what the body uses- doesn’t relax all the
way down to the baseline
b. Complete (fused)- not something that is seen in the body
naturally- lockjaw- muscles have gone into fused tetanus- will
fatigue very rapidly- this is what we did with our frog
2. How does tetanus involve calcium?
If stimulation is occurring at a fast enough frequency then the
amount of calcium in the cytoplasm the amount of calcium
starts building up because the pumps can’t pump it back into
the SR fast enough- the more calcium in the cytoplasm the
more binding of muscle fibers
T. Length- Tension Relation
1. Optimal length, lo : Put a little tension on frog before start- instead of a
totally relaxed muscle- the changes the length of the sarcomere- there
is a optimal length for the best muscle contaction- sometimes too short
or too long- in the middle there is a plave where 100% tension is
developed so want to stretch muscle so that they are at the optimal
length- if no place to bind there is no tension- no crossbridges because
too long therefore no tenstion- if too short overlap of actin- prevents
crossbridges from developing-at optimal length then it is perfect
a. A resting muscle is always at optimal length-this is for skeletal
muscle
2. Molecular basis- this helps determine optiaml length
a. Filament overlap
b. Troponin-Ca affinity decreases at short lengths- helps
determine optimal length- calcium cannot bind troponin easily
when the sarcomere is too short and actin overlaps itself

U. Whole Muscle Contraction

1. Control of muscle tension
2. Tension developed by each individual fiber (ways to increase tension_
a. A.P. Frequency (frequency-tension relation)
b. Fiber length (length-tension relation)- at optimal length
c. Fiber diameter – why- the greater the fiber diameter the greater
tension when the fiber contracts- a big fat muscle develops
greater tension- amount of tension developed depends on
fatigue
d. Fatigue- not being fatigue
3. Number of active fibers
a. Number of fibers per motor unit – the # changes depending on
size of muscle- Some motor units have thousands of muscle
fibers- others only have a few- a motor unit that will fire cause
all of its fibers to contract- if bigger muscle then get more
tension for less muscle fiber
1. Size of motor units affects degree of control
a. Ex: fingers small motor units tons of controls
b. Number of active motor units (recruitment)
c. More tension out of a muscle depends on motor units size and
how many are firing
4. Control of shortening velocity
a. Load on the whole muscle

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 1. Velocity will depend on load- large load slower than than
small load
b. Types of motor units in the muscle
1. Fast and slow twitch fibers- control of shortening velocity
depends on the fiber percentage
5. Recruitment
a. Because we know that the velocity will double if more motor
untis for load

V. Smooth Muscle
a. Found everywhere in your body all over the place- usually
changes shape and diameter of organ its is lining
b. 6 or 7 ways to make smooth muscle contract- depends on the
organ it lines
2. Involuntarily controlled- all the ways it uses to control its contraction
are involuntary- Extremely slow to contract and slow to relax
3. Blood vessels, digestive tract, bladder, uterus, eye- no real way to
fatigue these- this is GOOD- all have smooth muscle
4. Not attached to skeleton
5. No striations- reason because thinck and tin filaments are not pricisely
arranged in these
6. No troponin or t-tubules- none of these so different method of
controlling crossbrige cycle- don’t need t-tuble because so small- not
as hard to get things places through diffusion
7. Several different types of stimuli
8. Does have crossbridges- actin and myosin- with cycling like skeletal
muscles
9. No motor end plates
10. Some are tonically active
11. Uses low amount of energy and oxygen
12. Structure
a. Filaments
1. (Thick)
2. (Thin)
b. Anchored to dense bodies & PM
1. These mush up muscle like contracts becomes smaller
c. Oriented diagonally to cell axis
d. Not organized into myofibrils
W. Contraction
1. Sliding-filament mechanism
a. Similar to skeletal muscle
1. Smooth muscle has much larger optimal length range
b. No striations
c. Has optimal length- much larger functional range- much larger
optimal range
2. Functional range is greater than skeletal muscle
3. Contraction and Its Control
4. Cross-bridge activation
a. No troponin!
1. Changes how the contractions are regulated- in skeletal
muscle once tropomyosin and troponin- in smooth the

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 troponin never is blocking the way because there isn’t-
need a new way to control this
b. Controlled by phosphorylation of myosin (Ca++ regulated)
1. This is the way contraction of smooth muscle is
regulated
2. Need an increased in calcium can come from SR and
extracellular fluid (doesn’t come from anywhere but SR
in skeletal muscle)
3. Use calmoduli in the contraction of Smooth muscle Slide
6

X. Contraction and Fatigue

1. Slow contraction
a. Due to low myosin ATPase- this is good don’t use as much- this
is good
b. Slow Ca++ kinetics- have to pump out of cytoplasm these
pumps are SLO
2. No fatigue - WHY NOT?
a. Low shortening velocity
b. Latching (slow dissociation)
1. Can dephosphorylate mysoin heads, but they can hang
around and still be attached to actin- when they are
attached there is tension- the dephosphorylation does
not result in immediate relaxation when they are
dephosphorylated and still attached this is latch state
not using ATP not fatigue like (I think)
3. Relaxation occurs when myosin is dephosphorylated.
4. MLC phosphatase- causes dephosphorylation(?) of myosin head (or
phorphorylation)
Y. Sources of cytosolic calcium
1. The sarcoplasmic reticulum
a. No t-tubules - why doesn’t this matter?
1. Muslce skinny too little to need the T-tubles- small fiber
diameter- T-tubles quick to get muscle to contract, but
don’t eed this in T- tubles – depolarize cell membrane
the SR will release calcium (T tubles similar need
deplarization for them to release Ca into muscle fiber)-
coltage sensitive Ca channels in SR (in some smooth
muscle)
b. IP3 - second messenger- receptors on some muscle fibers- G
proptein- IP3 will cause calcium channels in SR to open- not all
smooth muscle will have both channels- signal transduction
mechanism
2. Extracellular calcium entering the cell through plasma-membrane
calcium channels
a. Voltage-sensitive calcium channels
1. On plasma membrane- not only on SR but on plasma
membrane to get from extracellular fluid
b. Calcium channels associated with chemical messengers
1. Also chemical messenger binding sites on surface of the
cell- cause opening of nongated calcium channels
- Permeability to calcium increases – 10000 times more
Ca outside cell
c. Caveolae- look like little cytotic vesicles- have calcium in them

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 and also have calcium gates on them act exactly like SR but are
very small- either chemical or messenger binding
3. Calcium actively transported back out of cytosol
a. Slower than in skeletal muscle
1. Pumps on both membrane and SR
4. Smooth muscle tone
a. Low-level contraction due to Ca++
1. Not the same as latch state
2. Low level contraction is due to constant release of
Calcium left in cytoplasm at all times- probably want this
to happen in sphincter muscles- also in arterioles –
diameter of arterioles are almost always at rest in and
intermediate diameter size (can be fully relaxed with
larger diameter or contracted with small diameter)-
don’t want to have max blood flow or least blood flow at
all times so have an intermediate value so can have
increase or decrease of bood flow
Z. Membrane Activation
a. Looking at memebrane potential these membranes undergo
Action potentials- Do not use Sodium ions to bring positive
charge into cell
2. Calcium ions (NOT sodium ions) bring + charge into cell- calcium ions
call rising phase of action potential- they depolarize the membrane-
have voltage gated calcium channels in smooth muscle membrane-
Small change in membrane opens voltage gated calcium channels and
then calcium comes in
a. Graded changes (these cause small changes in membrane
potential)
b. Don’t need Action potential to get calcium released
3. Spontaneous electrical activity
a. Pacemaker potential- some type of smooth muscle cells that
have this (slide 11)
b. There are leaky channels that allow leakage into cell at all
times- this is one kind of smooth muscle
c. What causes it?
1. Spike cause by calcium channels opening
4. Neurotransmitters released by autonomic neurons
1. Release by autonomic nervous system
b. No motor end-plate region
1. Was half way inbetween skeletal muscle
2. Receptors all over surface of smooth muscle cell- no
specific place for binding (slide 14) in autonomic nerve
have areas all along the neuron that can release
neurotransmitters- sit in vesicle in vericosities- Action
potential will move down nerve when it comes to place
with vesicles they will be released- there are receptors
all along smooth muscle fivers
c. Varicosities
1. Don’t have synaptic bulb have varicosities that are all
along synaptic neuron- these have vesicles with
neurotransmitter in them that are released when an
action potential reaches them
d. Both hyperpolarization and depolarization
1. Some neurotransmitters do these it depends not on the

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 neurotrasnmitter, but it depends on what receptor the
neurotrasmitter binds too- it’s the receptor that is
important not the neurotransmitter
e. Norepinephrine – released by sympatheic nerves-
neurotrasnmitter
1. Excitatory in vessels- vasoconstriction with
norepinephrine
2. Inhibitory in intestine- smooth muscle of intestines
relaxes with norepinephrine
5. Hormones (EPI)
a. Epinephrine will bind to receptors on surface of smooth muscle
and cause different effects
6. Locally induced changes (paracrine agents, acidity, oxygen
concentration, osmolarity)
a. Paracrine agents- ecosinoides are paracrine agent- can cause
smooth muscle contraction
b. pH change
c. Oxygen concentraton cause smooth muscle to contract or relax
d. Osmolarity will control whether it contracts or relaxes as well
7. Stretching
a. Some smooth muscles will be contracted by being stretched-
they will have mechanosensitive receptors in wall (linked to an
ion channel) when stretched will cause ion channels to open
and then have smooth muscle contract- can be a protective
thing- if stretched too much
AA. Types of Smooth Muscle
1. Single-unit smooth muscle
a. Has gap junctions protecting the cell – acts like one muscle cell-
all the cells contract as a unit because conneted by gap
junctions
b. Single units are found in intestine uterus and small vessels
c. Electrically linked, pacemakers, sparsely innervated- have both
sympathetic and parasymatchtic nervous system- have
different things that cause them to contract
2. Multi-unit smooth muscle
a. Each fiber must be stimulated by itself acts alone not as one
unit
b. Not electrically linked, no pacemakers, richly innervated
1. Have parasympathetic and sympathetic
c. Hairs, ciliary muscle, bronchi, large arteries
1. Muslce that make hairs stand on end- ciliary muscle in
eyes

BB. Overall Design of Cardiovascular System

1. Pump and vessels
a. Closed circulatory system
b. 2 circuits basically
1. Pulmonary
2. Systemic
2. Blood flow
a. Rapid flow of blood through the heart produced by pressure of

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 these two circuits
b. Blood exerts pressure on blood vessels- the harder the heart
beats the greater the pressure on the tubes exerted by the
blood
c. Bulk flow= fulids all flowing in one direction- how it moves in
the arterial system all parts of blood move in one direction all
together
d. Millions of miles of capillaries- every cell in body are within mm
of a capiilary bed (except maybe skin)
e. At any time only about 5% of blood is in the capillaries
f. Purpose of cardiovascular system carried out by capillaries-
transport nutrients- gases- and pick up wastes
1. Nutrients do not move out of capillaries by bulk flow-
moves into interstitial fluid- goes from interstitial fluid
into cell- things move by diffusion or some sort of
mediated transport (diffusion needs concentration
gradient) not an issue for blood in vessels
3. F = ∆ P/R
a. Blood flow is F
b. Between two points- change in pressure divided by resistance
4. Pressure
a. Hydrostatic pressure mm HG- pressure exerted by any fluid on
its container- measure in mm HG taking hydrostatic pressure of
blood in vessel cuff is around- needs to be a difference of
pressure from point A to point B
b. Pressure greatest near the heart because pressure is generated
by the heart
c. Pressure is always expressed in arteries- blood pressuere is
arterial pressure- highest point is in the Aorta
d. Fluid moves from higher pressure to lower pressure- how bulk
flow works
5. Resistance ®- resistance up blood flow down
a. How difficult it is for blood to flow between two points
b. Friction generated
c. Viscosity of a fluid (hematocrit)- viscous fluid more friction
resistance goes up- hematocrit makes blood more viscous-
dehydration more viscous
d. Length of the tube- shorter tubes less friction- longer the tube
the more friction therefore more resistance- more blood vessels
are needed when people have a large change in weight-
1. Heavier people need more capillaries
2. Not affect anything really on a daily basis
e. Tube’s radius (major factor)
1. Big vessel little resistance- little vessel lots of resistance
2. Resistance to flow= 8L η / pi*r 4
3. η = Viscosity
4. Radius of tubes change every day
CC.Cardiac Muscle
1. Myocaridum- heart muscle- wall of heart
2. Features:
a. Striated
1. Caridac muscle in microscope
2. Arrangement of thin and thick filaments causes this

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 b. Contraction stimulated by depol. of PM
1. If you depolarize the PM of one caridac muscle the next
one’s PM will be depolarized because of gap junctions
c. Cells connected by gap junctions
1. Gap junctions- similar to single unit smooth muscle cells
are connected by gap junctions
2. Electrical signals move through these
d. Conducting system
1. Myocaridal cells
2. Don’t contract
3. These initiate the action potentials and spread the action
potential- other muscle systems don’t have this
DD. Heartbeat Coordination
1. Cardiac action potentials (in contracting cells!! Ventricular) in the
Plasma Membrane
2. NONCONDUCTING CELLS
3. SLIDE 6******
4. Starts flat because permeability of ions stays the same
a. The Ventricular myocytes (not only ventricular also atrial)
1. NO pacemaker potential
2. Steady resting membrane potential
3. -85 mV- almost at potassium equilibrium
4. Much more permeable to potassium than sodium
b. Positive-feedback and sodium channels
1. Have a depolarized period slow repolarization- huge
increase in permeability to calcium- as the cell starts to
repolarize calcium channels are opened causing the cell
to remained depolarized for a longer period of time
c. Plateau of depolarization - Why?
1. Plateau of depolarization is caused by the opening of
coltage gated calcium channels*- they are a little slow in
opening, but they open and stay open for a londer period
of time to keep the cell depolarized- THIS IS IMPORTANT-
LASTS 0.3 seconds- refractory period in myocytes is 0.3
myocytes- can’t be stimulated rapidly- no summation-
no overstimulation- no fatigue- that’s good
2. Long lasting voltage gated calcium channels- long
lasting channels- sometimes called L channels
3. Not seen in SA cells
d. Calcium channels
1. Voltage-sensitive- same as L channels- long lasting
channels
2. Slow channels
e. Potassium channels
1. Decrease in permeability
2. Beginning high potassium permeability- leak channels
3. Leak channels close when the cell depolarizes
4. Second set of potassium channels to open are voltage
gated ones- the closing of the leak channels cause the
drop in permeability of Potassium
EE. Ventricular contracting myocytes
FF. Heartbeat Coordination
1. Action potentials in conducting system

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 a. SA node- All the nodes not just SA
1. Nonresting –resting potential
b. Pacemaker potential- slide 8
1. The resting potential- not flat- always changing
2. Permeability of ions is changing
3. This will bring this to threshold
4. Will have about 100 action potentials per minute
5. Parasympathetic will keep our heart rate from being 100
beats per minute
c. Automaticity – capacity for spontaneous and rhythmic
contraction- heart will beat on its own outside the body with
special solutions- heart transplants will chill them and keep
them from beating
d. What is responsible for pacemaker potential?
a. Potassium channels closing
b. Funny channels- like it negative- sodium
c. Transitory calcium channels that will open when
membrane is negative
2. Progressive “spontaneous” reduction in membrane
permeability to potassium- K channels spontaneously
close
3. Small progressive increases in the permeabilities to
Na2+ and Ca2+
a. F channels voltage gated channels- open when
membrane is most negative (funny channels)
b. T type- transitory- calcium channels- Calcium
coming in is part of the depolarization
e. Once threshold is reached calcium influx cause the
depolarization of the membrane in the conducting system not
sodium*- no long lasting calcium channels in conducting
system- they shut very quickly these long lasting calcium
channels are coltage gated – potassium back in cause
repolarization

GG. Sequence of Excitation (slide 10)

a. Action potential just goes from cell to cell to cell
2. SA node depolarization normally generates the current that leads to
depolarization of all other cardiac-muscle cells
a. Depolarizes without influence from other cells – 100X per
minute
b. If SA node is detroyed AV node will take its plave, but the AV
node is much slower-
1. AV node can depolarize on its own, but it have AP from
SA node it is depolarized before it can be depolarized by
itself
2. Pacemaker potential is almost unnecessary in AV node
3. SA’s discharge rate determines the heart rate
a. SA node depolarizes faster than the rest of the conduction
system
b. If the SA node is not in charge then will have a different
pacemaker thing take over and have a slower rate
4. WHY?
5. If activity of SA node is depressed or blocked another portion of the

17
 conducting system can take over as pacemaker
a. Delay in AV node- the delay is so that there is enough time for
atrial contraction before the ventrical contracts- AP slows down
at first in AV node then speeds up again
b. Contraction of ventrical starts at the apex- squeezes from the
bottom up- want to push blood toward Aorta – out of ventricle
HH. Sequence of Activation
1. A.P. spreads from SA node to atrial syncytium (syncytium- cells
connected by gap junctions that contract as a unit)- 2 separate
syncytium
2. A.P. spread to ventricles via atrioventricular node- slows down a little
3. A.P. enters wall of interventricular system via bundle of His- bundle
branches to R and L ventricles
4. Bundle of HIS divides into right and left bundle branches
5. Purkinje fibers (spread contraction to) pass activation to ventricular
myocytes
II. The electrocardiogram
a. Tracking electrical events going through the heart
b. Action Potentials of cardiac muscle cells
c. Charges throughout your body
2. P wave- picking up current of the artia starting to contract- atrial
depolarization
3. QRS complex- major thing that is happening is depolarization of the
ventricle- also there is artia repolarization
4. T wave- repolarization of the ventricles
a. Between the S-T segments can show what can be a problem
with heart
JJ. Excitation-contraction coupling
1. Sequence of events
a. Depolarization of plasma membrane
1. Increase is cells cytosolic calcium
b. Spreads along T-tubules- have these in skeletal and caridac
muscle
c. Voltage-sensitive Ca2+ channels in T-tubules open- this makes
voltage gate calcium channel in SR to open and release
calcium- Dihydropuradine and ryanadine
1. Voltage gated calicum channels in T tubles- let calcium
in from outside
2. The calcium coming in stimulates the release of calcium
from the SR
d. This Ca2+ stimulates Ca2+ release from SR- Calcium should
make heart contract really hard if added more than already has
it
e. Rest similar to skeletal muscle- calcium binds to troponin etc.
etc.
KK. Strength of cardiac muscle contraction dependent on cytosolic
calcium concentration
1. Differs from skeletal muscle- Skeletal muscle contraction not
really dependent on cytosolic calcium
a. More calcium more tension developed
LL. Refractory period of heart (slide 15)
a. Blue is contraction and relaxation of the muscle

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 b. Even as muscle is relaxing can’t even restimulate it
before it is fully relaxed
2. No summation or tetany
a. Why not?-
1. Can’t restiumlate muscle soon enough
b. Why is that a good thing?
1. No fatigue

TEST LIKES TO HAVE US COMPARE & CONTRAST MUSCLES

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