June 14th 2007 -Lecture 3 - exam 2

muscle
review-
we have skeletal muscle oragans that are surrounded by a connective tissue...that connective
tissue is an epimysium..like a dense connective tissue....skeletal muscle organ is a big bundle of
fasicles...all of these fasciles ar esurruneded by that epiymsium.... these muscle fasicles are
surrounded by perimysium ct, its still a dense ct, each fassicle is made up of circles called
myofibers or muscle fibers, these are all muscle cells, so a bundle of muscle cells is called a
muscle fassicle and its surrounded by perimysium.
-you take an individual muscle cell and u take it out and u look at also called a myofiber also
called a muscle fiber, it has a connective tissue called endomysium surrounding it..its more of a
loose connective tissue but it has a bunch of little circles in it called myofibrils, so this myofiber
whichi s a muscle cells has myofibrils...and we know that the myofibrils break down even further
into myofilaments. we know that the myofilaments (thick and thin filaments) arrange themselves
in repeating units that make up myofibrils that are called sarcomeres.
This loose connective tissue has a bunch of cappilaries( this are the smallest blood vessels we
have) and nerve fibers that are going to be synapsing with the muscle cell, controlling it
voluntarily throught our consience commands, some stem cells some satellite cells some
myoblasts hanging out there as well. these cappilaries get larger as u move up to different levels,
and they actually peirce into the muscle at a specific levels, so we have larger blood vessels,
arteries and veins peircing into muslce branching down into arteriols and venioles and all the way
down to the cappilaries down in the muscle levels, these cappilaries are nurishing these muscle
cells keeping htem alive,
the nerves are controlling htem
we said a muslce cell is a synsishum, a fusion of many cells the cells are stem cells called
myoblasts and therefore they are multincleate there also striated muscle cells that means they
have sarcomeres. it has a banded like appearance , dark and light bands
we said taht the plasma membrane of a skeletal muscle cell is called a sarcolemma ,and the fluid
we find inside the cell is called sarcoplasm(same as cytoplasm), we said invaginaition in the
plasma membrane deep into the interior of the cell are called t tubules(aka transverse tubules)
-the resting membrane potential(REM) of the cel is -85 mv (more negative on the inside than the
outside) so if you want to excited this muscle cell you need to depolarize it to -70 or -60 or -50
you have to make it more positive or less negative, when u excite a muscle cell it responds my
shortening(thats the only thing it can do), it shortens from the smallest structural units all the way
up, saromeres shorten, myofibrils shorten, fassicle shorten and the whole muscle cell shortens ..
all the muscle cell makes up muscle organs so the whole organ shortens. the only thing muscle
knows how to do is shorten,,,and hte only thing u can do to a muscle cell is excite it, you cannot
inhibit a skeletal muscle cell naturaly (there are certain toxin and drugs taht can) - they are loaded
with mitcohondria bc these cells are doing alot of respiration(whether it be fatty acids or a glucose
molecules or a muscle wasting disease maybe they are using protein for energy) but they are
using primarily fat and glucose for cellular respiration so taht they can make atp
- they have alot of glycogen stores , these glycogen stores are for that purpose they want to do
phosphorylysis reactoins and spit glucose out and use that glucose for cellular respiration, they
can use creatin phosphate if htey want, pop a phosphate off of creatin and use that for energy as
well
-the organelle taht is surrounding all these myofibrils this specialized organellse we find in
skeletal cells is called a sarcoplasmic reticulum and its function is just to store calcium
-myofibrils are bundles of myofilaments(thick and thin filaments - thin - primarily made up of actin
- thick - primarily myosin) when myosin and actin assemble themselves together they form these
units that we call sarcomeres, and when u line up sarcomeres end to end to end u form myofibrils
so a myofibril is a repeating unit of sarcomeres
-SR is analogous to smooth ER but it doesnt do waht smooth ER does it just stores calcium (the
sr that is)
-if u have 2 peices of terminal systerni these dilated regions of SR and T tubule u have a triad,
now the signal to contract is going to be a depolarization along the sarcolemma that will travel all
the way down the T tubule, and now that signal is in close proximity to that organelle called the
SR and when u excite the membrane of the SR it releases calcium, and calcium will be the
signalling molecule for actin and myosin filaments to interact with one another, when they interact
muscle will contract.
so in order to store calcium in high concentration the sr specifically in the terminal systerni
regions has a protein called cacliquestrin right in the mb of the organele itself , calciquestrin
stores calcium (***calciquestrin is different from calcitriol or colcalciferol)
in the longitudinal region of the SR we find pumps to get the calcium back in the SR we call them
calcium atpases or caclium pumps (same thing)
-pic of it - skeleteal muscle cells with a bunch of holes in it , theholes are invagination for t tubules
and the things in yellow are the t tubules and they all interconnect together adn the fluid floating
inside will be interstitial fliuid(extracellular fluid) **the fluid running thru the t tubules is NOT
sarcoplasm** the t tubule is actually part of the sarcolemma (looking from the outside)....inside
teh tube is close to SR but looking at the t tubule form the outside ur not close to the SR....so the
point is to have the plasma membrane in close proximity to the SR....when the membrane of the
SR gets excited it spits calcium out all over these myofilaments and when u dump calcium on
myofilaments they slide past one another, normally they cant ,they cant interact wiht one another
but once u put calcium there they slide past one another and the muscle contracts
-pic of myofibrils - sarcomeres repeating .....looking at thin and thick filaments (myofilaments)
and u see that they are arranged in structures that are called indeed sarcomeres, u see thick and
thin filaments
-sarcomeres are structures taht are made up of myofilaments , they are the smallest structural
and functional unit of msucle that is made up of myofilametns (thick and thin) ... is sarcomere
smallest structural and functional unit of all mucle? TRUE OR FALSE? ====FALSE bc smooth
muscle dont have any sarcomere
- muscle contraction will result from the interaction of these myofilaments (thin and thick) ..but in
order for these filaments to slide past one another u need proteins to help stabalize these 3d
structures these sarcomeres thru stabalizing proteins and u also need regulatory proteins that
regulate interactions btw thick and thin filaments, if htey interact all day long then ur going to
contract all day long so u need a regulatory protein to make it so that they normally dont contract
but somehoe u can allow them to interact so that they do contract....
htey ive the b anded appearance to muscles - the A(dark) bands and the I(light) bands and pic of
sarcomere - m line in the middle and u have thick filaments or myosin protien radiating out from
that and outside there is a big frame work of actin and thats a z line and ther are thin filaments
running in towards the thick fialments
-muscle does not act actively its passive .....actively the frame work of thick and thin filaments is
moving in
- zones and bands
h zone is distance btw one thin filament and another filament
a band is the length of the myosin filament
zone of overlap is hwerehver thin and thick filaments overalpping one aonther
i band - disntance btw the end of one thick filaments and the end of ano ther thick
filametns(adjacent sarcomere) - so half of an i band in one sarcomere and the other half in an
adjacent sarcomere
- myosin framework not moving but jsut the z disk coming closeer together and all the thin
filament coming closer together
-myosin f ramework not moving and the thin framework is moving in closer bu thick filament iwl
move eventually - actin moves relatively to myosin
-when a sarcomere contracts what happens to the Hzone? - it gets smaller bc the thin filaments
are going to proximate one another
-when a sarcomere contracts what happens to the Aband?- doesnt change...its the length of the
thick filaments taht never changes
-when a sarcomere contracts what happens to the I band? - it gets smaller bc even tho the
sarcomere in themiddle is contracting the other sarcomeres beside it are going to contract
-the whole myofibril is going to shrink in like an acordian and al the I bands are going to get
smaller
-when a sarcomere contracts what happens to the zone of overalp? - its going to get larger bc as
the thin filaments move relative to the thick there is going to be more overlap...the more overlap u
have the more overlap u have btw thick and thin filaments, the more interaction the more tension
u generate muslce.....
----in a relaxed muscle actin and myosin myofilaments lay side by side and the h zones and i
bands are at maximum width, during contraction the actin and myosin myofilaments interact the
actins are pulled towards the center of each myosin myofilament as a result the sarcomeres
shorten... in the fully contracted muscle the ends of the actin myofilaments overalp the h zones
dissapear and hte i bands become very narrow
-light micrograph of msucle - u can see i and a bands....bunch of sarcomeres in a bands u ahve
thick and thin filaments and in an i band u have only thin filaments and thats why a bands are
dark bc they ahve both typs of bands including thick filaments
-endomysium is on the outside of sarcolemma . -endomysium is made up by fibroblasts (a
connective tissue) u also find myoblasts hanging out in endomysium
-fibroblasts made the connective tissue that makes up endomysium ( the loose connective tissue)
-another look as a sarcomere and u see what is present at varoius regions along a sarcomere - u
look at a z disk and in a different plane and the z disk is called a z line..i ts the same thing, its just
a difference in planes....u see alot of actin filaments (thin) and ualso see the protein that Titen
protein it attches to the z disk
-they are also sayin there is abunch of actinin filaments , alpha actinin is the protein that attches
thin filaments to the z disk....
point of cnfusion -ACTININ ATTACHES ACTIN TO THE Z DISK
-present in (were always talkin about relaxed sarcomere- u could argue that if u find a sarcomere
that is completely contracted there would be tons of thick filaments packed in there) ....
-Titen is an elastic protein taht helps preveents sarcomeres from over stretching
-lookin thru and I band u find thin filaments and u find titen (of relaxed sarcomere - if it was
contradted u would find thick filaments too)
-m line - u find myosin proteins all inter connected together
-there isa protein like actinin that connects myosin to the m line caled myomesin ---
myomesin connects myosin filaments to the m line
-h zone = u see myosin filaments and in side the myosin filaments u see titen filaments - so that
means titen filaments dont attach to the end of myosin it runs right thru the core of it and attaches
to the m line...so yes u find myosin but u find titen right in the center of that myosin filament
-u could argue that u can find thin filaments if the sarcomere was contracted...its not its
relaxed
**the most imp zone = zone of overlap....we find a bunch of thick filaments and a bunch fo thin
filaments..u could look at it in 2 different ways - 1- u could say we hav 6 thin filaments
surrounding one thick filaments - 2- or u could say there are 3 thick filaments surrounding one
thin....best way is - u have myosin filament in the middle and u have a bunch of head groups
sticking out and htey are binding to all theese thin filaments and they are dragging these thin
filametns, whats really oging to happen is when ur looking at this cross sectional view, picture
myosin filametns stayin in place and picture all the toher ones (red) being pulled out towards
u....myosin proteins have all these head groups pivoting dragging all the red filaments out of the
screen towards u
-thin filaments are not just made up of actin...primarily they are made up of actin but there is more
their....now were looking at a z disk and where the thin fialments attach and u can see titen
attching ot the elastic protein and u can seee that if a sarcomere was jerked on and stretched it
would recoil back.... facilitated by tthse titen filaments
-u see thin filaments - u see actinin attching this thin filament to the z line ..... the 2 strings of
beeds is actin...so the primary component is actin.....it looks like 2 strings of beeds,, we call them
actin monomers, each individual glob is called a G actin and they dimerize together 2 + 2 + 2 + 2
.....+ 2 get togheter and they form these 2 strings of beeds that we call F actin and the f stands for
filamentous .......long filamentous protein -- so what makes up a thin filaments - primary thing is
actin not g actin..g actin is a sub unit but the resaon we have to talk about g actin is becuase
each individual g actin has this active site to it and thats imp.....
-2nd protein( ther are 4 that mkae up thin filament..........1st was Factin)-----protein running in the
middle Nebulin...and that protein facilitates the dimerization of all the g actin into f actin....
-other 2 proteins are just regulatory proteins -(3rd protein) troponin and (4th protein)
tropomyosin.....
-tropomyosin is a long filamentous protein, this does not run along the entire length of a thin
filament....Nebulin does... NOT tropomysin..tropomysin only runs the length of about 7 G actin
monomers and then it stop and another one picks up and runs the length of another 7..so there
are a bunch of tropomysin molecules all throught the thin filaments
Troponin - there is only 1 troponin (complex) for every tropomyosin molecule....so u dont see
troponin riddled along the thin filaments like u see tropomysin
-troponin does 2 things in general : - binds to tropomyosin -binds the thing u have been storing in
your sarcoplasmic reticulum : calcium
- tropomyosin is the protein that (in a relaxed state) covers all hte active sites on the g actin
monomers......when u release calcium, calcium binds to troponin and troponin undergoes a
conformational change, when that happens it pulls on tropomyosin and it pulls it out of the way
the way and it exposes all those sites now all the active sites on actin are exposed......whast are
the active sites active for? - the binding of that..
- if u look at thick filement- u can see taht there abunch of head groups sticking off....a bunch of
gold clubs with the handle a ttached to the M line and the head of the golf club just facing
outwards in multiple directions bc its 3d, and u see all the myosin head groups all pointing
towards the Z disk right now, in a relaxed sarcomere they are pointing towards the Z disk
-all the myosin head groups have an affinity for that active site and if htey bind to the active site
they will change conformation...if cacliumb binds to troponin, troponin wil pull tropomyosin out of
the way and expose those active sites, myosin will bind to actin on the monomers, and it will pivot
from one state to antoher( f acing towards the z disk to now facing towards the m line meanwhile
its takin this whole framework and dragging it toward the m line
-so its the myosin head groups pivoting thats draggin the thin filaments towards the m line.... ---
sliding filament theory
---myofibrils - in relaxed state -- u see d ark / light bands - u see m lines - .........contracted - m
lines and z disks move relatively together [contractions -myofibrils shorten]
-we have a bunch of myofibrils hanging out - sarcoplasm of the cell(myofibrils are loaded inside
sarcoplasm) - these myofibrils are doing this all day long they are are going from one state to
antoehr - all your myofibrils are shortening and shortenin . how is it that the sarcolemma is
shortening? ...if your myofibrils are shortening ....u have a cell with a bunch of myofibrils in it just
shortening but why is it that the enitre cell is shortening..tahts the purpose u excited that cell bc u
want the entire cell to shoten...somehow someting has to happen ...something has to exist...what
is that? there needs to be some kind of attachment of the myofibrils to your sarcolemma... if your
myofibrils are attached to your cytoskeleten , now u can shrink the sarcolemme, if u shrink the
sarcolemma your fassicles will shirnk and muslce organs will shrink, your have to have somekind
of attachment, the protein that attaches these myofibrils to your plasma membrane is called
DYSTROPHIN....now u cann understand
if somebody has muscular dystrophy there could be a problem with muscle contraction , if the
gene coding for dystrophin is not present bc their myofibrils are not attahched to their plasma
membranee , essentially tahtts going to be paralysis
-review slide - look at it....epimysium to sarcomere - it shows u that ur terminal systerni is
dumping caclium right over the zone of overlap wihci is nice
-detail about muslce contraction -
--ANIMATION - theysay that this nerve fiber is synapsing with this muscle cell ...and when it
synapses with the muscle cell its goign to release a neurotransimitter called acetocholine - it
excited the muslce cell. that excitement will go all the way down the t tubule and it wil rub off on
the SR ..when it does this Ca wil be released into the sarcoplasm (zone of overlap) causin
calcium to bind to troponin . troponin will pull tropomyosni out of the way, expose the active sites
and now myosin can bind to actin
-thin filaments - 2 strings of beeds - troponin and tropomyosin ,,,, nebulin is runnin thru the
center .... u see myosin head groups pointing towards z disk, they are wanting to bind to the g
actin but htey can bc tropomyosin is blockin that ..... so add caclium ...to troponin..then troponin
pulls tropomyosin out of the way....thne myosin binds to actin and myosin pivots and whne it
pivots actin is pulled
- atp comes in and it breaks the cross bridge.....for power of muscle contraction - atp is NOT
used....atp is just used ot break the cross bridge
...ca can be removed = if u remove it - the active sits cover up, myosin cant bind a nymore and
we have a relaxed sarcomere
-contraction of skeletal muslce
- muscle fibers generate a tension (same as force) ,,, which is transferred to a tendon...so the
muscle shortens in one plane, and it happens to be that the tendon taht it a ttached to the muscle
( really that came from the muslce, it came from epimysiom and perimysium) it has all DRegC ct
fibers that connects to the bone so it pulls in one direction...whatever tension is on the muscle is
applied to the bone...and if wahtsever on the bone the load that is, is less then the tension
generated in the muscle it will move,,,,if the load on hte bone is Greater the the tension in hte
muslce then it wont move
EQN FOR BONE MOVEMENT - IF TENSION IS GREATER THAN RESISTANCE THEN THEIR
WILL MOVEMENT .... IF TENSION IS LESS THAN RESISTANCE THEN THEIR IWLL BE NO
MOVEMENT
- CONTROL OF SKELETAL MUSCLE CELLS - we can se that we have a neuron comming here
and it is arborizing .... terminating with the skeletal muscle cell sarcolemma...forming
synapses...its going to excite the cell..its going to go down t t ubule, calcium will be released,
thick and thin filaments are going to move relative to each other...and the mmuscle fiber is going
to shroten and therefore muscle organ will shorten..............when a muscle organ shortens it jerks
in on 2 dfferent tendons, and what it does is it pulls on 2 bones...we have an origin and we have
an inser tion...one bone pulling on will not move,,,tahts where it originates from , the bone thats
going to move when its tendon moves on it is where its inserting it at...
-control activity of seketel muscle
-central nervous sytem...voluntarily control....the axons branch in your perimysium so a nerve
fiber will peirce into your epymysium .....but once in gets to perimysium it will start branching off, it
will start terminating as synaptic knobs (note - terminal knobs are only found in endomysium bc
the terminal knobs is what is synapsing with your muscle cell ) a muscle and nerve intercellular
connectin is just a type of synaps...so when a nerve cell and muscle cell interact we call it a
synaps.......if a nerve cell and a nerve cell interact we call it a synaps too...also called a neuro-
neuro junction........nerve cell and mus cle cell ewe call i t a neuro-muscluar junction
---were looking ata neuro muscular junction ......weer lookin at a nerve fiber coming out of our
CNS synapsing with our muscle clls and forming neuromuscular junctins(nmj)times called
myoneurojunctions....nmj is the abreviation....
3 things that make up nmj:
1-a terminal knob of the neuron
2-motor m plate of the mucle cell
3- space btw the two called synapitc cleft
now we know that the pm of a skeletal muscle cell is called sarcolemma...but the region of the pm
that is ............that terminal knob of a neuron is called a motor m plate...so the motor m plate is a
specialized regoin of the sarcolemma....nw if thot that a synpatic cleft and synaps are the same
thing then u wer inccorrect they are totally diffeerent...the synaps is a connecting btw 2 cells
..synaptic cleft is the space btw that terminal knob and motor m plate
-synaptic celft contains what? - interstitiay fluid (its on the outside of cel so )
myofiber - banded like appearance....
-it is motor neurons that is controlling skeletal muslce cells - specifically -- somatic motor neurons
-
- 2 major divisions of nervous system
-1-somatic nervous system - controls skeletal muscle
-2- autonomic nervous sytem - controls everything else...everythng eles is smooth muslce cardiac
muscle and glands maybe e ven fat muche ...w/o our conscience con trl
---synaptic terminal and terminal knob is the same thing
-motor neurons are multi polar neurons ....efferent - carries info form the CNS to the
PNS........affereent - infor towards teh CNS ....this is efferent info
the cell bodies of these neurons are located in the brain and spinal chord....not all of the control
of your muslce comes from brain...there is a significant amount of control of skeletal muscle that
comes from your spinal chord....so cell bodies are in your brain and ur spinal chord....fact -
walkng is controlled at the level of spinal chord...not controlled by brain,, ...still cel lbodies and
there still motor neurons( still cns) but spinal chord
-axons are located in the peripheral nervous system insiee our nerves (cranial and spinal) the
synapitic terminals are located in the muslce the terninal kknobs are located in endomysium....pic
of effferentmulti neuron.....u cant telll that its efferent bc efferent is someting thoelogical or
function... but tis multi polar this means taht if thats ur cell body it has many processes radiating
out form it...in many diff diriections...u will find neurons with one process radiatin off its body =
unipolar neurson....2 processe s - bi polar nurons....
axon perices right into mucle cell and branches in perimsyium once.... it gets to endomysiun it
forms terninal knobs that form synaps... right on sarcolemme
synaptic knob-terminal knob- terminal button- terminal buton - al same thing....we usuallysay
synaptic terminal....lots of names
muscl cell -big cell, long fibrous cell,...mulitnucleate cell, have myofibrils, sarcomeres, but here is
pm the sarcolemma and in this specific region folds up
-motor m plate increases surface area....for wat? - for absorption...but not here but we increase
surface area to have more of something...not absorption but so we can have more receptors for
the neurotransmitters cming out of the nueron...so more pm then more rec eptors ...called ACH
receptors...ach is abreviation of the neurotransmitter tahts going to bind the receptors -
acetocholine (ach) .....
-looking at terminal knob or synaptic terminal of hte nuerons u wil see that it contains alot of mb
bound vesicles aclled synaptic terminals...which is why its good to call it termina knob or synaptic
terminal bc waht u find in it is synaptic vesicles....
-when the nerve fires action potential.....(excited...consiencly comand it to) these synaptic
vessicles will undergo exocytosis...when they do this they dump all that acetocholine out....and all
hte ach will bind to all the ach receptors...al that ach will be diffusing thru that interstitial fluid and
bind to all those receptors..
ach is an excitatory neurotransimitter.....neurtransmitter...then excited neurotransmitter....its not
always excited but in the nmj it isALWAY excited..
itsthe only neurotranssmitter u will find in a nmj........acetocholine....again..the only thing u can do
to a skeletal muslce cell is excite it... the only thing in its synaptic cleft is an excitatory
neurotransmitter
-electrolyte imbalance causes musce lcells ur cramp up..........charli horse?
-synaptic vessicle releasing neurotransmitter - acetocholine....and its inding to receptors on the
post synaptic cell.......... cell before synaps- pre synaptic cell .. cell after synaps - post synaptic
cell....
the stimulus for thse vessicles taht undergo exocytosis is calcim coming in...calcium coming into
that knob stimulates that to happen....
-everythign that happen in the neuron results in calcium coming in so that a neurotransmitter can
be released...everything
-neurotransmitter released it binds to the post synaptic membrane to the acetocholine
receptors.....
-an enzyme found in the cleft also found in the mb of the skeletal muscle cell - achE in an enzyme
that degrades acetacholine - its called acetocholine Esterase....
it degrades it all day long...so no off and on switch..any why acetocholine works is bc ther is more
acetocholne being produced than achE so ther is nnot enuough ach E to degrade all that ach at
one time...so as its degrading ther are some ach's that are being degraded so the signal stil gets
across...it sitl binds to receptors...its only a millisecodn to bind ... .then achE degrades it and
removes ach from its receptors....
- if achE didnt exist and u stimuilate nerve cell and u release ach and it would stay there....if it
stayed ther then as soon as ur muscle contracted it would never relax... the first step for a muslce
to relax is for u to stop telling it to contract and then the nerve wil stop firing action potential then
the ache will chew up all the ach .. if get ach off a receptor the muscle clel will relax and
uncontracted,,,,ache is always there alwyas degrading but more ach released then the ache can
handle at once...but it catches up eventually...but after being cheewed up by achE the
compounds that make up ach are taken back up and they rebuild the ach....
-we can call the receptor many things...1- nicotinic receptor bc it binds nicotine...2-cholonergic
receptor bc ach binds to it 3-ligand gated sodium channel - more commonnly...a ligand is a
signalling molecule....the ligand is ach in this case
-ach binds to recepotr and excites it...another toxin binds to it ...a plant alkaloid (qurary?) ...it
binds to nicotinic receptor ..its an analog to ach...it binds JUST liek ach but the problem is that it
does not function like ach.....it doesnt allow sodium to ocme in to the cell and excite it....it
competitively inhibits the binding of ach and it clogs up receptors...when it cloges the receptors
that means the transmission is gone normally ach binds to receptor and excites muslce cell...if
quaray is bound to all the receptors than ach cant bind...this means qurary is not exciting hte cell
its not allowing the receptor to do its job....what happens is the muscle cell is paralized ( by
inhibition the receptors in motor m plate....
-ther is another way to do this...by toxin = botulinin toxin - it gets in to blood and interstitial fluid
and it gets taken up by terminal knobs . it prevents production of ach and if cant make ach ...u
can fire action potential all day long...ach will nvr be released its nvr goin to bind to receptor and
the muscle will be paralized
- botulnin is responsible for waht we call PREsynaptic blockade............qurary is responsible for
POST synaptic blockade....blocking transmission presynaptically -botulinin -------------blocking
transmission Presynaptically
- diff forms of botulinin toxin - some more lethal then others (more potent) ---------- a concetrated
tea spoon could kill e ve ryone on the planet....... but some kind is weak
the weaker stuf is waht we use for BOTOX...and the whole purpose of this is to paralize
muslce...we want to prevent neurons that are attached to our muscle cells - specifically the
muscle underneath skin that looks wrinkled...bc the skin looks wrinkled bc the muscles are
tonically contracting and when they tonically contract the skin shrivels up...so what we wana do is
we want to paralize the muscle so that it is relaxed all the time...if its relaxed all the time then the
skin stretches out and it wil give a lesser appearance of winkles
=pic
[ach receptor is a receptor / channel ...when ach binds to receptor it opens and it lets ions come
in the cell
------------------showing action potential being spread along ur terminal knob as it does its Ca
comes in stimulates the synaptic vessicle to release ach . ach binds the ligand gated sodium
channel and na comes in to cell....achE eats up all ach and degrades it...and now ur back to
rest....[note. the reason why we call it ligand gated sodium channel is bc its gated my a ligan
-ach- when ach binds the gate opens and na comes is,,,,
-rem of muscle cell = -85 mv...what do u thin happens to that -85 when sodium comes in - it gets
more postive and less negative - reducing polarity - depolarizing = excitation - 60 really
excited...........excitemnt spreads al lthe way dwon t tubule ca is relased....then ca binds to
trop............................
-image of nmj..................ligand gated na channel = chemically gated cation channel...........
it actually takes 2 ach to bind to receptor for it to open and allow ions in..........-note - in teh motor
m plate thats the only thing u find is ligand gated sodium chanel
-ligand gated channe;- the channel is also permeable to potassium but ALOT more permissive to
sodium than potassium .... so much that the K lving is irrelavent...
-when Na comes in here ..its makin cell -80 or -75...but taht is not an a ctuall action potential..it is
not spreading all over pm...it does not reach all the way down to t tubules.....an action potential is
a change in mb potential propagated all the way along the pm.......it not happenin here...when na
comes in here it depolarizes the cell where it comes to...if sodium comes in antoher place ... that
place will get depolarized ther.....wherever there is a ligand gated channel the cel will be
depolarized right beneath it...but its not spreading....so the only thiing u get in an M PLATE is a
LOCAL potential..LOCAL change in mb potential
-note - if u have ligand gated channel....thatas all u wil ever get - LOCAL POTENTIAL
- if u want the potential that will spread along the mb u need voltage gated channels....Voltage
gated channels are all along sarcolemma...and t tubules.... pm in muscle cell...everywerhe accept
m plate is voltage gated channels...this leads to propagation(an action potential).............if enough
sodium builds up outside the cell the gate opens...so this is was voltage gates channel means -
its a channel taht is usually close at a certain voltage....but when the voltage changes ...the
channeel opens... the voltaga at which the channel is closed is -85 mv....but if the the voltage
changes to maybe - 60 mv then the channel opens - theshold voltage - -60mv
-so if there are enough sodiums there to pop open the channel at - 60 ...sodium will come
in........the voltage gated channels are in series......all along pm sodium is in and all along t
tubules sodium is in.......this is a propagation
action potential - motor m plate.....lots of sodium in...then u see that the inside is more -ve than
outside bc the action potential hasnt reached it yet
-dyhydopuridine -DHP- receptor is located in t tubule and its sensitive to cahnge in mb potential
-if u look at SR in the systernal region..wehr ca is.it has a receptor too - RYANADINE
RECEPTOR - RY RECEPTOR....they dont bind nehting
-the action potential is propagated down pm down t tubules activated dhp and has connection to
RY receptor and pulls taht door open calcium comes in binds to troponin ..... tropponin pulls
tropomysin....myson pivots and moves the z line towards the m line
-we know that there is a connection btw the dhp and the RY receptors ....but dont no exactly the
mech of the connection...but thers connection do exist in lik the ear ...
-RY IS OPEND BY DHP bc an action potential is reached down to the t tubule
Skeletal msucle cell
axon , terminal knob, motor m plate , ach, and when sodium comes in the action ptoetnal jumps
along the pm but it doesnt really JUMP ...so sodium coming in...ca is being released by dialted
region of the terminal systerni (sr) and is dumpd in zoen of overlap
last page of cell lec
-in pm of skeletal muscle ecll ther are things resp (2) for generating a -85 millivolts = 1-k leak
chanles - 2- na/k channel...
-------waht is present in a t tubule = 1-k leaak channels 2- na/k channels 3- DHP receptor
m plate ? - k leak nak pump .....Ligand gated chennles
point is - once the si gnal is removed here and all the ligand gated na channel is closed taht cell
needs to reppolarize back to -85 so taht u can stimulate it again......how does it repolarize? by k
leak channels and also nak pumps and now its ready to by stimulated again by neurtransmitter
-here is ca released from SR ...it shows ur thick and thin filametns and u see the active site of g
monomers nad u see tropomysoin is blocking the active site but if put ca there then active site is
exposed...and the myosin is pivoting
- so we have a resting sarcomere- .....myosin head groups are facing AWAY form the m line and
TOWARDS TEH z discs
in a relaxed myosin head group, it has 2 things bound to it -ADP and Pi (inorganic
phosphate)...what help the P on to adp? - energy....what is in head group? - energy.....keeps it
pivoted away from the m line...u can see that tropomyosin is blocking the active sites....wehn
calciujm the active sites are exposed...myosin then binds to actin bc it has affinity to it ther is a
conformationalchange which causes adp and Pi falls off whihc causes head groupd to under go
conformational change which causes the myosin head groups to pivot toward the m line
what is resp for power stroke of muscle contractoin? - it is the loss of adp and Pi that casues the
head group to pivot toward the m line
if uwant to break the dross bridge................it stuck pivoting toward the m line...so what u have to
do is to break the cross bridge...atp comes in and splits it (breaks the cross bridge = which is
waht we call myosin bound to actin - a cross brideg)
note- NO conformational cahgne when atp binds to head group, it still faces the m line it just
release it self from actin... it is when atp hydrolyses into adp and pi and puts energy into the head
it cocks back away form m line toward z disk
-cross bridge cycling
how do we know atp only resp ffor breakin cross bridges and not resp for power stroke? bc we
know a conditon called rigor mortis - u have stiff ...bc muslces are jamed so they are stiff bc the
myosin head groups are stuck to actin filaments bc the individual that is stiff is not respiring
anymore...if not then no atp . no atp then cant break cross bridges
summary