Physio Bio 336 Notes

5-21-14
Phosphate has a positive and a negative charge
Phospholipid by layer has water outside Extracellular fluid and the inside is intracellular
fluid
Diameter of phospholipid bilayer is 6-10 nm
Water is polar. Water interacts with polar phosphate heads. Intracellular water
Lipid tails are hydrophobic (dont interact with water)
No charges on lipids
Olive oil is hydrophobic so it doesnt mix with water
Phosphate heads interact with polar water on outside and inside
Proteins in phospholipid bi layer= are integral proteins
Weight of membrane is 50% weight is phospholipid bi layer and 50% is integral protein
Intregal protein are either gates/channels
Gate is opened/close
Intregal proteins can help things move from ecf to icf
Voltage gated sodium channel= channel (is protein embedded in phospholipid bilayer)
that allow sodium to move through
Proteins are highly specific
Proteins can also pump things from high to low concentration
Sodium Potassium atpase
Latin word for sodium is natrium which is where Na comes from
Hyponatremia
Hypo= low
Emia= in the blood
Hyponatremia= low sodium in the blood stream
Hyperkalemia=
Hyper= high
Kalium= latin for potassium
Positive charged= cations= t looks like plus sign
Anion= negatively charged
Sodium and potassium are cations
Sodium potassium atpase
Ase= an enzyme system
Enzymes catalyze most chemical reactions= proteins that make reactions go much faster
ATP= adenosine triphosphate
Chemical energy in ATP bonds
Kcal= most common form of energy= amount of energy required to raise 1 L of water 1
degree Celsius
Apple has 100 Kcal means you can raise 1 L water 100 degree Celsius
ATPase= breaks bond and energy is liberated which has the atp sodium potassium pump
3 Na out and 2 K in= ATP broken down to ADP + P + 7.3 Kcal (energy) = we have
energy to pump 3 sodium ions out and simulataneously 2 potassium ions come in
Sodium/potassium atpase is an integral protein embedded in cell membranes and takes
energy
Membrane has to be fluid= so proteins can move= gates have to move so pump like a
gate has to move to pump potassium and sodium= this is called the fluid mosaic model=
2 things that are different between extracell fluid and intracell fluid
ATP Na/k pump requires 25% BMR
Cells are constantly pumping sodium and potassium in and out
High sodium in extracellular fluid. Normal for Human beings 135-145 mmol/L
concentration of Na+. 140 mmol/L need to know this middle number
Hyponatrimium= blood sodium concentration 130 mmol/L
Normal Inside concentration of Na+ = 12 mmol/L
Sodium wants to diffuse back in because 140 mmol out and 12 mmol in
Sodium cant diffuse back in because membrane is made up of phospholipid bilayer, only
way for sodium to get in is by a gate
Ex. Dilutional hyponatremia= people on roller coaster and kept drinking water. The
mother drank too much water. ECF with Na the sodium would get diluted
Ex. Consumption hyponatremia= is when you dont eat enough sodium
Congestive heart failure= store more water= edema= so get hyponatremia from extra
water
High amounts of potassium inside cell because sodium/potassium atpase pumps
120 mmol/L on inside is potassium
3.5 to 5 mmol/L on outside is potassium
Hypokalemia has blood levels of potassium lower than 3.5
Hyperkalemia= levels above 5 normal range is 4
Sodium ions cant go in because cell membrane is not very permeable and sodium
channels are not open
Some proteins gates/channels, some pumps, receptors that can bind to other substances
Protein embedded in human cells called potassium ion leak channel, intregal protein in
membrane of human cells, allows only potassium to move, called leak channel because
the channel is opened all the time= 120 mmol of potassium on inside and 4 outside
(because of sodium potassium atp ase pump) so potassium wants to go diffuse from high
conc to low conc, so as potassium ions go out of cell the inside of the cell becomes
negative (-80mv) across the cell membrane, this negative charge pulls potassium ion back
in, this causes the resting membrane potential, potassium is thus at electrochemical
equilibrium ( which means that potassium is both going in and out simultaneously which
happens in a resting cell)
High sodium outside of cell,
Part 2 Lecture
5-21-14
Electrochemical equilibrium is for potassium and not for sodium (not permeable at
rest)
Integral membrane protein which is potassium leak channel allows potassium to be
permeable
If potassium was uncharged it would equilibriate equally
Resting Membrane Potential= all alive cells= -80mv
Two british physiologist Huxley and Hodgkin took a giant axon of the squid, cut
squid open and got a big nerve which is 1 mm in diameter, high sodium outside cell,
high potassium inside cell (electrochemical equilibrium), they were able to take
electrodes much smaller than diameter of cell, measurage voltage between two
electrodes, if electrodes are both in extra cell fluid it is like both are on positive and it
reads 0, they took 1 electrode and moved it down into ICF which read -80mv which is
RMP, won nobel prize,
Before 1960 did not know squid had giant nerve cells. Did not make little electrodes
Resting potential in human nerves and muscle= -80 mv (what causes it
Inject huge amounts of potassium in bloodstream= hyperkalemia, no longer at
equilibrium which stops heart, destroy RMP, much less diffusion, dead
5-22-14 P.1
Resting human cells are not permeable to Na
Potassium is permeable in resting cell
140 mmol of Na outside/ 12m mol inside cell
Sodium wants to go from high to low but cant because it is not permeable to Na.
Potassium 4mmol outside the cell
Potassium wants to go from high to low
Hodgkin and Huxley took small batteries and ran wire into axon
0 mv means exactly same negative and positive inside as outside of cell
-80 mv means few potassium diffused out
Add +30 mv little battery, goes from 80 mv to -50 mv
Life is action potential
To have heart beat you need action potential
Pain is action potential, so is taste, movement
In human beings threshold is -50 mv which will cause action potential to occur
Cells are -80 mv are polarized because there are excess negative charges on the inside
which means excess positive charges on the outside
Across the cell membrane the cell is polarized
0 mv means that the cell is no longer polarized
At rest it is polarized with RMP of -80 mv
Depolarization means to take polarized state away because the cell is no longer polarized
Depolarization means to bring cells closer to 0 mv
+30 mv (overshoot) means that the inside of the cell is positive with the respect to the
outside
Repolarization bring back to RMP which is -80 mv
Hyperpolarization means to be more negative than resting which is -90 mv. After
hyperpolarization we go back to RMP
Action potential takes 3-4 milliseconds
Blink of eye is 40 milliseconds
Lots of Na outside cells lots of K inside cell.
Protein in cell membrane
1. Sodium potassium atpase (high sodium outside high potassium inside which costs 25
% of daily energy Resting Metabolic Rate, potassium and sodium are used to create
action potential)
2. Potassium Leak Channel (generate RMP)
3. Voltage gated sodium channel (generate AP)
4. Voltage gated potassium channel (generate AP)
All integral proteins
-80 mv voltage gated sodium channel is closed
At threshold -50 mv which means voltage gated sodium channel opens which means
sodium goes inside the cell because there was high outside to low inside. This means that
the sodium ions that are cations cause the voltage inside the cell becomes +30 mv.
Voltage gated sodium channel stays open for 1 ms
-50 mv threshold of the voltage gated Na channel
In 1ms Na ions rushed into the cell and the cell has depolarized and overshot to +30 mv
Depolarization and overshoot to +30 mv takes 1 ms because voltage gated sodium
channel stays open for 1 ms. At +30 mv the sodium gate closes. Simultaneously the K
voltage gated channel opens at +30 mv (integral protein).
You needed more K+ in cell so at +30 mv when the potassium channel opens the
potassium goes out of cell. As potassium goes out of cell the inside of the cell repolarizes
back to -80 mv.
K+ of 75 mmol outside and inside. The opening of the channel allows it to move.
Potassium moves because of diffusion which is going from high to low concentration.
This person with K+ of 75 inside and out has hyperkalemia.
Voltage gated Na channel stayed open for 1 milli second at -50 mv stayed open til it got
to +30 mv
Voltage gated K channel stays open for 2 milli seconds. Within one milli second the
voltage gated channel potassium would repolarize back to -80 mv which is where it does
not close. The Voltage gated K channel closes at -90 mv which is 2 milli seconds.
Hyperpolized= more polarized which is critically important for moving action potential
which is why 1 milli second would make us dead. Is the ECF same as blood? (question
for professor).
-90 mv is where both potassium and sodium voltage gated channels are closed
At rest both K and Na voltage channels are closed
You need high amounts of K inside cell so it could diffuse out so you can repolarize cell
Because Na rushing in causes depolarization
Hugkin and Huxley
1. first to stick electrodes inside cell and measure Resting Membrane potential
2. stick wire attached to small batteries in cell and see pattern of action potential
3. set up two electrodes (one in ICF and one in ECF) which measure voltage difference
across the cell membrane, stimulated it got action potential, at rest before they did
anything the voltage read -80mv RMP
Action potentials can move across the cell (this is called conduction along the cell)
Speed at which action potential moves is called conduction velocity (which on average is
1 meter/sec for most muscle and nerve cells)
Need to make action potentials move faster than 1 meter/sec
Soma aka cell body, nucleus located inside cell cody (membrane enclose cell body and
membrane is made up of phospholipid bilayer where on neuron in phospholipid bi
layer(question)?
Dendrites stick off cell body in nerve cells to greatly increase surface area
5-22-14 Lecture p.2
Human Neuron
1 axon to 10 collaterals to 1:1000 collaterals
Each collateral has a terminal button
Voltage Na and K channels= generate AP
Cell body and axon come together at the axon hillock
Axon hillock is the first place where there are voltage gated Na and K channels
Soma and Dendrites dont generate actional potentials because there are no voltage
gate Na/K channels
Action potential thus first occurs in axon hillock and moves from soma to terminal
buttons or collaterals (moves 1 m/s which is conduction velocity which is too slow)
Human neurons have myelin that wraps around the axon
No myelin on soma or dendrites because there is no action potential thus no
conduction velocity
Gap between each piece of myelin is node of ranvier
Node of ranvier is where cell membrane is in contact with ECF
Myelin means that Na and K cant cross the myelination
Voltage gates are only on nodes of ranvier (because the other voltage gates are stuck
under myelin)
Unmyelinated neuron conduction velocity is 1 meter/sec
Mylinated neuron velocity conduction is 100 m/s (called saltatory conduction)
increase conduction velocity
Dictance from one node to another is 1 millimeter
You cant myelinate the whole axon because the Na voltage channel would not reach
threshold thus would not open
Demylinating disease= takes myelin off= conduction velocity would be really slow=
100 times slower
1. most common disease= multiple sclerosis (autoimmune disease which means you
cant catch it and its not contagious), antibodies dont recognize myelin and so they
destroy myelin, ( symptoms: arm/ leg paralysis and vision problems)
2. bacteria= diphtheria
3. heavy metals (mercury, arsenic, lead) poison with these
Madhatter syndrome refers to heavy metal poisoining
Madhatter = hats made of mercury= which poison people and make them go crazy
Action potential takes 3 milliseconds
Next action potential at node of ranvier
Myelinated neuron has higher conduction velocity
Collateral and terminal button of neuron will almost touch the next neuron
50 nm distance (synapse)
Phospholipid bi layer was 10 nm
Terminal button come down to dendrites is called a synapse
10,000 synspes on a cell is wrong
8,000 of synapses = terminal button to dendrite (80%)
2,000 terminal = button to soma (20%)
Action potential is electrical going from axon hillock
Synaptic transmission turns electrical signal (actional potential) to chemical which
helps to cross synapse which generates another action potential which is electrical.
5-27-14 Lecture P.1
Cell body called the soma
Dendrites greatly increase surface area for more synapses
No action potentials at soma and dendrites
Get axon hillock to -50 mv which is threshold for opening voltage gated Na channels
action potential in non myelinated is 1 meter per second
myline is a fatty sheet, there are gaps called nodes of ranvier which is where AP will
occur
cant have AP at myelination because you cant open the voltage gated Na/K channels
because of myelin
AP jumps from next area to next area is salutatory conduction (neurons that are
myelinated)
Color of myelin is dull whitish color
Wherever there is myelination is white mater
Axon to collateral ratio is (1:10, 1:100, 1:1000)
Area that are myelinated in neuron are axon and collaterals
White matter where myelination is include axons and collaterals
Myelin around terminal buttons means chemicals cant get out
Terminal buttons synapse with another neuron
Grey matter means non myelinated areas which are dendrites, soma, and all of the
terminal buttons (wherever synapses are occurring), synapses dont occur in white matter
The AP of myelinated is moving 100 meter/sec
Diseases that demylinate include coordination issues because AP is too slow (supposed to
travel 100 m/s)
Suffix system for drug identification
Suffix tells class of drugs
Caine drug = are local anesthetics= block voltage gated Na channel =
Lidocaine = binds voltage gated Na channels and blocks these channels so there is no
pain = only lasts a couple of hours= how long it lasts is how fast lidocaine is washed
away (which means AP is generated again)
To make ligocaine last longer you should reduce the blood flow by using epinephrine
Epinephrine causes vasoconstriction (reduces blood flow) means that the lidocaine does
not get washed away
You need to be careful with ears, nose, toes, fingers, and penis (be careful injecting
epinephrine with lidocaine because they dont have good blood supply)
Oraverse causes vasodilation (open)
Puffer fish has inside it a toxin called tetrodotoxin works like lidocaine and blocks the
voltage gated Na channels
Animal
Cone snails have a harpoon and fish comes along and they harpoon it so the venom has
conotoxin and block the Na voltage gated channels
Fugu is puffer fish = eat enough to make lips and tongue go numb because tetrodotoxin is
blocking the voltage gated Na channels = too much means all Na voltage gated channels
get closed
Terminal button (unmyelinated) synapses with dendrite (unmyelinated), this is gray
matter in the brain because they are unmyelinated
AP is electrical which we need to turn it to chemical
Nerve AP, chemical signal in muscle (acetyl coline), Nerve AP
Longitudinal fissure separate left and right hepispheres of the brain
Between brain and spinal cord is a structure called brain stem (made of midbrain, ponds,
and medulla)
Medulla connects to spinal cord
For every muscle there are two neurons that connect it
Two neurons have to synapase
We have upper motor neuron that goes to medulla and crosses over to medulla from right
to left, decends down into spinal cord, and axon ends in collaterals to terminal buttons
Terminal buttons of the lower motor neuron and the skeletal muscle is called
neuromuscular junction
Outer surface of the brain is gray matter because cell bodies are out there where there is
no myelination
Outer surface of brain is cerebral cortex (grey area outside brain)
Cortex in latin means bark of the tree which is outside
Inside of brain is white matter because it has myelination in it
AP at left bicep, AP starts in right motor cortex, because Upper motor neurons decosate
(means to cross) at level of medulla, so damage in right motor cortex (paralysis on left
hand side),
Contralateral = side of injury side of paralysis are opposite
Ipsilateral = side of injury and side of paralysis are same side
http://en.wikipedia.org/wiki/File:Blausen_0103_Brain_Sensory%26Motor.png
If you have injury in right motor cortex symptomology is contralateral paralysis of left
hand structures
Injuries above medulla produce paralysis that are (pons, midbrain) = contralateral
paralysis because injuries above decusation causes contralateral
Below medulla injury= ipsilateral paralysis because it is already decussated
Upper Motor Neurons in human being= Decusation means to cross which occurs at the
level of the medulla
Lesion means damage to the tissue by disease, bullet, physical damage, cancer
Lesion above the medulla result in contralateral paralysis
Lesion below medulla result in ipsilateral paralysis
Frontal view of brain = can see longitudinal fissure
Central sulcus= sulcus means groove
Fissure means big groove
Logitudinal fissure is between the left and right hemisphere
Central sulcus is a groove
Infront of central sulcus is frontal lobe, area behind central sulcus is parietal lobe of the
brain
Area infront of central sulcus is the frontal lobe and includes the motor cortex
Just infront of central sulcus is the motor cortex
All of the upper motor neurons are not located all over the brain
Upper motor neurons are located in the cerebral cortex
Portion of the cerebral cortex that the upper motor neurons are located in is the motor
cortex which is located in the frontal lobe directly anterior of the central sulcus
Upper motor Neurons are arranged in a homunculus
Homunculus means simply little man
HAL the homunculus = Head, Arm, Leg
http://upload.wikimedia.org/wikipedia/commons/c/c4/1421_Sensory_Homunculus.jpg


Upper Motor neurons in the superior region of the motor cortex intervate the arms
Upper motor neuron that intervate the left leg would start in right hemisphere (c answer),
right motor cortex ( b answer),
Lateral portion is where head/face is
Medial or middle portion closest to the longitudinal fissure is where the leg is
Lesion in medial left motor cortex? Symtomlogoy? Contralteral leg paralysis
Face paralysis stroke cant move right side of face? left motor cortex in the lateral aspect
of motor cortex
Contralateral paralysis in arm and leg damaged where (x marks spot)? (question) where is
the damage occurring if you have this type of paralysis?
Arm leg and face paralysis (x mark spot)? Question where is the damage occurring if you
have this type of paralysis?
Hemiparalysis= half of a side paralyzed
Face arm and leg paralysis all left side = left hemiparlysis
Out of spinal cord are 31 pairs of nerves coming off either side which are spinal nerves
12 nerves come off brain and brain stem and these are the cranial nerves
Spinal nerves are below the medulla
12 nerves above medulla are cranial nerves
The first 8 that come off are cervical spinal nerves (C1-C8)
http://media-cache-
ec0.pinimg.com/736x/29/80/fd/2980fd335e8b10ba89470cc29f7a4b7e.jpg
Thoracic are where 12 ribs come off (T1-T12)
Spinal nerve 9 is T1
T12 is 20
th
spinal nerve
5 lumbar region nerve (L1-L5)
5 COMING OUT OF SACCRYL (S1-S5)
COCCYGEAL (CO)
31 SPINAL NERVES COME OFF SPINAL CORD
Spinal nerves made up of
Upper motor neurons are not leaving the spinal nerves
Upper motor neurons leaving spinal cord? = no. Start in motor cortox end at lower motor
neuron
Arm Muscles nerves coming out of (C5 to T1)
Leg muscles intervated by (s3-s5)
Spinal cord injury at T10 you can still move your arms in the cervical nerves
Spinal cord injury go across T10? called parapalegia. Can get actional potentials above
the injury so you can move arm
Injure at C3 quadrapalegia (injuries above c5) because arm muscular is
White matter= corona radiata is where all upper motor neurons for that hemisphere (head
,arm leg) come together
When upper motor neurons come together it is called internal capsule which is white
because it is made up of myelinated axons of the upper motor neuron
Internal capsule goes down to the medulla
What happens at the medulla is where decusation crosses
Now the upper motor neurons travel down spinal cord and the portion that they travel is
called the cortico (motor cortex) spinal tract is where the upper motor neuron (already
decussated)
If you had gun shot wound to left cortico spinal tract (completely destroyed above C5)
symptomology? = ipsilateral paralysis of legs and arm is it because quadrapalegia
(injuries above c5)what side would be paralyzed?(question)
Any injury from corona radiate to the medulla = result in complete hemiparalysis because
all of upper motor neurons come together in capsule
5-27-14 Lecture P.2
Corona radialis/ interal capsule is white
Internal capsule at medulla is still white
Synapses occur in gray matter
Synapses are terminal buttons come very close to dendrite regions (gray matter)
Cell bodies of upper motor neuron are in motor cortex
Axon of upper motor neuron is in corona radiate and internal capsule
Lesion in left cortico spinotract at T10? Symptomology? = ipsilateral paralysis of left leg
(why left leg is it because of the decusation from the right side?) this is parapalegia?
Upper and Lower motor neuron synapse occurs in ventral horn
5-28-14 Lecture P.1
Starting with upper motor neuron order of descending is: Cell body, mylinated axon,
corona radiata, internal capsule, midbrain, pons, mediulla, decusates at medulla, come
down CST, synapse with lower motor neuron, which synapses with skeletal muscle
C5-T1= intervate the arm
Below T1 intervates the leg
Synapse between lower motor neuron and muscle = neuromuscular junction
Lesions (aka injuries) Above medulla =contralateral
Lesions (aka injuries) Below medulla = ipsilateral
Below T1= intervate the leg
C5-T1= intervate the arm
Car accident damage left cst and right cst at T10? Both of them (CST) damaged =
parapalegia
Damage one side= ipsilateral or contralateral
Injured at T10 would it be hemiparlysis? No because you can still get action potential up
at C7 (intervates the arm) which is above T10. Hemiparlysis is paralysis of leg, arms, and
head of one side.
Hemi means hemisphere (half)
http://towerorthopaedics.com/images/spine_anatomy.gif
Cortico spinal tract (CST) is apart of spinal cord
Lidocaine, tetrodotoxin,. Conotoxin block voltage gated Na channel
Nerve to nerve synapse = spinal cord
Nerve to muscle sybnapse = NMJ
Action potential to the muscle = muscle will contract
Synaptic transmission= how action potentials can get across synapses
Neurotransmitter = acetyle coline generates muscle Action Potential
Nerve action potential (electrical) > chemical (acetyl coline) > Nerve Action potential
(electrical)
Where is start of upper motor neuron makes left muscle contract? In superior motor
cortex of right hemisphere
There is a phospholipid bilayer around the terminal buttons and the sarcolemma
-80 mv inside terminal buttons and the sarcolemma
Inside terminal buttons are vesicals (phospholipid vesicles)
Every phospholipid bilayer has proteins embedded= proteins coming off are v snare
proteins= v stands for vesicles
V snare proteins are located in the phospholipid bi layer of the vesicles
Inside vesicles are acetyl coline (10,000)
Acetyl coline = acetic acid + coline
Proteins on terminal button are T snare proteins
T snares and V stares have high affinity for each other so V snares come down and join t
snares (docking
Docking is when v snares and t snares are hooked together and bring the vesicle close to
membrane
Action potential arrive at terminal buttons because they conduct
Concentration of Ca++ (cation) is 2 mmol/L on the outsider of cell (ECF)
Intregal membrane protein embedded in terminal button
6 intregal proteins
1. Na/K atpase
2. Voltage Gated Na channel
3. Voltage Gated K channel
4. K leak channels
5. Voltage Gated Ca channel
6. T snare
Action Potential arrives at terminal button and voltage goes from =-80 mv to +30 mv
because Na ions are rushing in which opens voltage gated Ca channel
Voltage gated Ca channel is located in terminal botton of neurons
Ca is going to diffuse from high to low into the cell and as it diffuses there is a protein
Vesicle is made of phospholipid bi layer, two proteins embedded (T snare and
synaptotagmin (question) are these two proteins on the vesicle? Where is v snare?
Confused where v snare vs t snare is located?
Synaptotagmin is a intregal membrane protein embedded in the vesicles
Voltage gated Ca/ K channel both open at +30 mv
Potassium going out of cell at the same time Ca ions go in terminal button and bind to
synaptotagmin
Binding of Synaptotagmin and Ca coming in which causes synaptotagmin to insert in cell
membrane of terminal button and now docked vesicle (pulled down) membrane of
terminal button (pulled up), fusion pore opens and acetyl coline is released
Vesicle and membrane of terminal button are made up of phospholipid bi layer. Ex. Stick
of warm butter and another stick of warm butter and smushed them means they blend
which is analogy for vesical and membrane coming together like sticks of butter
Instead of blend the scientific word is exocytosis
Exo means out because acetyle coline can diffuse out into synapse between terminal
button and sarcolemma
Synaptotagmin waits for Ca
Steps of action potential to chemical
1. action potential (opening of voltage gated Na channel) get to neuromuscular junc
2. Action potential causes open voltage gated Ca
3. Ca diffuses into the terminal button
4. Ca bind to synaptotagmin
5. Synaptotagmin inserts into membrane causes membrane and vesicle to fuse (fusion
pore)
6. Allows exocytosis of acetyl coline (neurotransmitter)
Release acetyle coline = muscles contract
Venom black widow spiders use, venom is protein that inserts itself into membrane of
cells (phospholipid bilayer of terminal button), allows cell to become permeable to Ca,
Ca enters which cause exocytosis and causes the muscle to contract
Two types of paralysis, flaccid paralysis (soft, when muscle isnt moving at all),
spasmotic paralysis (uncontrolled)
Bitten by black widow spider, the venom has a protein which starts in cell membrane and
Ca then goes inside uncontrollably, synaptotagmin is binded to Ca, this causes exocytosis
(Va gated Ca channel opens is the only time when Ca goes into terminal button when you
have action potential), equals spasmotic paralysis
Clostridium botulinum makes toxin and is anaerobic, eat peaches, toxin enter terminal
buttons which cleaves or destroys t snares and v snares, non of the synaptic vesicles are
not docked so you cant have exocytosis, all of this means that you have flasccid
paralysis
Clostridium botulinum causes respiratory distress
Dermatologists can take Botox and inject into muscle which does nothing in muscle
because there are no v snares and t snares (located in terminal button), inject into muscle
it goes backward and destroys v snares and t snares which in turn causes flaccid paralysis
Takes 6 weeks for t snares and v snares to be rebuilt
Back spasms, botox stops spasiming, destroys v snares and t snares which prevent
exocytosis so which results in flaccid paralysis
5-28-14 P.2
Membrane of muscle is phospholipid bilayer
Sarcolemma is phospholipid bilayer of skeletal muscles
Terminal button from lower motor neuron synapses with sarcolemma is called motor
end plate
Invaginated motor end plate increases surface area and so the chemical signal binds
On motor end plate there are protein receptors called nicotinic ach receptor
Nicotinic ach receptor has acetyl coline and nicotine that can bind
Nicotinic ach receptor are intregal membrane proteins embedded in motor end plate
High sodium outside, high potassium inside, acetyl coline diffuses after they have been
released, distance between synapse is 50 nm, acetyl coline comes from vesicles which
exocytosed and goes to synapse and binds to nicotinic ach receptor at the motor end
plates, when acetyl coline binds the nicotinic ach receptor opens and allows Na ions to
diffuse through the receptor\
Nicotinic ach receptor( is a sodium ion channel), what makes it open is acetyl coline, this
is a ligand (means a chemical not voltage), as Na+ diffuse into cell there is depolarization
to -50mv which opens voltage gated Na channel (causes more Na+ to rush in), makes
+30 mv
Synaptic transmission 1. Exocytosis 2. Action potential in muscle
Voltage in muscle is -80 mv (voltage and nicotinic receptors are not open)
Chemical back to electrical
Nerve Action potential, open voltage Ca gated channel, Ca diffuse in, Ca binds to
synaptotagmin, erxocytosis, release acetyl coline, acetyl coline diffuse across synapse
which binds to nicotinic ach receptor which opens and allows Na to diffuse into cell
which depolarize the muscle cell to -50mv (threshold) which open Va Na channel,
and Na goes in and takes it to +30, channel open for 1 millisecond, the Va K
channel opens and potassium rushes out goes to -90 mv, and generates AP
Threshold= AP
Curarea blocks the nicotinic ach receptors
Agonist/Antagonist
Antagonist= binds a receptor and stops it from working (aka blockers), block intended
agonist from binding
Agonist for nicotinc ach receptor = Ach
Antagonist for nicotinic ach receptor= curarea
Monkey with curarea is going to die of flaccid paralysis because the nicotinic ach
receptors are blocked with curarea and so acetyle coline cant bind, therefore there can be
no action potential in the muscle, can cause respiratory paralysis (cause muscle have been
paralyzed)
Curarea they put in tube so you can breath and not die of respiratory failure
Curarea lasts 15 mins
alpha bungarotoxin is a nicotinic ach receptor antagonist (flaccid paralysis), respiratory
paralysis forever
5-29-14 Lec p.1
We are allowed to use abbreviations on
Essay fill out front and back of 8 by 11 piece of paper
How many synapses does AP have to cross to get from motor cortex down to skeletal
muscle? Motor cortex to skeletal muscle (cross two synapses)
Proteins in terminal button are t snare
Vesicles filled with acetyl coline
8 nm is distance between vesicle docked and the membrane at terminal button
Ca binds to synaptotagmin and it inserts into cell membrane of terminal button which
leads to vesicle and membrane = fusion pore, leads to exocytosis of acetyl coline
Skeletal muscle fiber which has underneath synapse is motor end plate which contains
proteins called nicotinic ach receptors
Voltage inside is -80mv (at rest)
Need to turn chemical back to electrical
Acetyl coline bind to nicotinic ach receptor and opens, allows Na ions to diffuse into cell,
muscle cell reach threshold= AP (muscle AP)
Black widow spider venom causes uncontrolled Ca which normally gets in through
voltage gated Ca channel, so get continual Ca and exocytosis so you have muscle spasm
Botulism destroy v snare and t snare, dont have v snare and t snare no dock so no
exocytosis, so no release of acetyl coline, so have flaccid paralysis
Nicotinic ach receptor antagonist (block from getting acetyl coline) 1. Alpha
bungarotoxin 2. Curare, binds to nicotinic ach receptor and blocks nicotinic ach receptor
from getting acetyl coline
You only want 1 Nerve AP to generate 1 muscle AP
To close ach receptor you need cholinesterase
Cholinesterase (break down Ach) is an enzyme so is Sodium/K atpase (breaks down
ATP)
Acetyl coline binds to nicotinic ach receptor for 1 millisecond (reach threshold) which
causes NA to reach threshold, cholinesterase is part of nicotinic ach receptor,
cholinesterase breaks Ach down, so the nicotinic ach receptor closes, to make muscle
contract again send another NAP
The cholinesterase takes 1 millisecond to break down acetyl coline
Cholinesterase inhibitor = which means nicotinic ach receptor would stay open (Na keeps
on rushing in) and you would have multiple MAP so you have spasmodic paralysis
Sarin Gas Ex Tokyo subway, people took in sarin gas and opened up, sarin gas is
cholinesterase inhibitor, couldnt get nicotinic ach receptor to close, so spasmodic
paralysis (diaphragm spasms then you cant breath so die from respiratory fail)
VX gas is worse than sarin gas, potent cholinesterase inhibitor,
Symptoms of vs gas
1. twitchy
2. spasms
2 PAM chloride, put on lateral side thigh, this reactivates cholinesterase
Durban is cholinesterase inhibitor
Autoimmune disease are 1. Multiple scolorosis (antibodies that demylinate) 2.
Myasthenia gravis (antibodies destroy nicotinic ach receptors)
Myasthenia gravis symptomology 1. Muscle weakness (destroyed nicotinic ach receptors
which stay open for 1 millisecond cause cholinesterase, depolarize only to -60 which
doesnt reach threshold, so flaccid paralysis) 2. Droppy eyelids 3. Lack of muscle
coordination
Treat person with myasthenia gravis with only 2 nicotinic ach receptors by
Healthy person have 4 nicotinic ach receptors, ach binds to receptors and makes them
open up, Na rush in for 1 millisecond, and cholinesterase break down, destroy half of
receptors, give cholinesterase inhibitor to keep the 2 remaining receptors open for 2
millisec, so same amount of Na goes in, drug given is neostigmine(small amount is
solution to myasthenia gravis) (pill so it cant disperse like gas)
Vx gas, sarin gas, Durban(solid form), and neostigmine = are all cholinesterase inhibitors
Person with myasthenia gravis that overdose on neostigmine would go to spasmodic
paralysis (open too long then there will be multiple MAP)
Dose makes poison
Bicep muscle of human being = 500,000 individual muscle fibers, 500,000 sarcolemma
(each muscle fiber has sarcolemma), 500,000 NMJ, motor end plates 500,000
http://anatomycorner.com/muscles/images/muscle_anatomy.jpg
Inside each sarcolemma are myofibrils (5,000 inside)
Sarcolemma surrounds the muscle fiber
Myofibril is striated,
Proteins in skeletal muscle 1. Structural 2. Contractile 3. Regulatory proteins (when to
contract and when to relax)
Sarcomere
http://kristinandcory.com/img/91/91c/Sarcomere_Contraction_Process_Of_Muscle_Cont
raction_With_Myosin_Actin.jpg
Myofibrils is made up of subunits called sarcomeres (dont confuse with sarcolemma)
Myofibril is striated because each sarcomere composed of myosin( thick protein) , 4 thin
proteins (actin), shine light means hard time getting through myosin, and can get through
actin easy (cause its thin)
Dark at myosin, and light at actin
A band is dark (represent length of myosin), I band (light)
Striated muscle = dark/light pattern
5-29-14 P.2
Contraction of skeletal muscle= sliding filament theory
Sarcomeres contracted vs. relaxed
http://classconnection.s3.amazonaws.com/33/flashcards/602033/jpg/11_sarcomere_band
_patterns_-_relaxed_and_contracted1311911754610.jpg
Resting vs Contracted: Myosin is the same, actin is the same
Actin gets slid over myosin molecule, sarcomere gets shorter (muscle contracts), A band
same, same Ex. Metal pointer sliding over each other like actin and myosin
A band same so the myosin hasnt changed size, I band much smaller cause actin and
myosin slide, Z lines get closer together, this explained by sliding filament theory
A sarcomere is one z line to the next z line
Contractile proteins, structural proteins, regulatory proteins
Actin and myosin are the contractile proteins (cause they slide over each other making
sarcomere become shorter)
Two structural proteins 1. Z line (made of protein actinin not actin, does not participate in
sliding, it holds actin in position over myosin so it can slide across it,)
Role of actinin is structural protein that holds the actin in position so it can slide
Without actinin the orientation would be incorrect which is that actin and myosin are
parallel to each other
Titin hooks from z line to myosin molecules
http://upload.wikimedia.org/wikipedia/commons/6/6e/Sarcomere.svg
Titin keeps myosin molecules centered within the actin, z-line (made of actinin) which
holds actin in place, the purpose of this orientation of titan and actinin is to keep the
contractile proteins actinin and myosin in a sarcomere manner
Coming off myosin at 90 degree angle to myosin molecule (perpendicular to myosin
molecule) are structures that stick up myosin head
Myosin head at rest: is at 90 degree angel to myosin molecule, not touching the actin
molecule (not cross bridged)
What happens to make the actin slide across myosin to shorten I band, and make
sarcomere shorter = Myosin head can hook to actin molecule and when it hooks it is
called cross bridging, the head will cycle in 4 steps cross bridge cycling
1. Cross Bridge (myosin head hooks onto actin)
2. Ratchet (Myosin head rotates to 45 degree angel) pulls actin molecule with it 10 nm
aka power stroke
3. Detachment
4. Recovers to original position 90 degrees, then Hooks Back again (10 nm from
previous)
Do this hundred thousand times you get actin to slide over myosin
Cross Bridge Cycling, each time cross bridge moves the actin molecule is sliding across
myosin (moves 10 nm which is the diameter of cell membrane)
One pull of cross bridge moves it 10 nm which would have to happen billions of times
for you to create a movement (Ex. arm to nose)
Analogy of cross bridge cycle = ore rowing
1. Myosin + ADP = high affinity for actin (myosin wants to bind to actin when atp is
hooked to it)
2. myosin + ATP = low affinity for actin
RESTING MUSCLE
1.90 degrees
2. not cross bridged
3. ADP hooked
Myosin head binds to actin with ADP hooked to it which is cross bridging, myosin
head pulls, ADP comes off and new atp hooks onwhich decreases affinity and it detaches,
ATP broken down to adp and energy moves myosin head to 90 degrees, so adp attaches
to myosin head again and cross bridging occurs and the cross bridging cycle repeats
Pet dies = rigor mortis (stiff death which takes 6 hours), not stiff only dead less than 6
hours
When you are dead= you are not making anymore atp, so myosin head can still bind with
ADP and heads pull to 45 degrees but myosin heads cant detach because there is no ATP
Rigor mortis = upon death ATP levels deplete in muscle all myosin heads get stuck at
step 2 cant go to step 3 of cross bridge cycle which happens in all muscles and the
myosin stays in a 45 degree angle and cant detach because no atp
Good pictures of what he talked about with muscle physio
http://www.slideshare.net/fullscreen/raniamansibang/muscle-physio/3