MSK phys Flashcards
toxin in puffer fish
tetrodoxin
what is given to Tx tetrodoxin poisoning
activated charcoal to bind it up
how does tetrodoxin work
block V Na Channels
inhibits depolarization
AP generation/propagation inhibited
blockage of K leak channels would do what
hypopolarize RMP
what toxin is in mamba snakes
dendrotoxin
how does dendrotoxin work
blocks V K channels so blocks hypopolarization
effects of dendrotoxin on Ach release
inhibit repolarization prolonging AP prolonged Ca influx at nerve terminal enhanced ACh release hyperexcitability and convulsive Sx
inheritance of malignant hyperthermia
autosomal dominant
what can trigger malignant hyperthermia
volatile anesthetics and some muscle relaxers
what causes malignant hyperthermia
uncontrolled release of Ca from SR leading to tachy, rigidity, hyperventilation and hyperthermia
acute hypermetabolic state in muscle tissue leading to prolonged contraction
what R is affected in malignant hyperthermia
RYR1
also could be dihydropyridine R
where is RYR located
SR membrane
what are the L type Ca channels and where are they located
DHPR
T tubule membrane
role of DHPR
voltage sensor
role of Ca in skel mm tension
removes regulatory protein tropomyosin from actin so there can be cross bridge formation
what is directly proportional to tension production in skel mm
number of cross bridges
what is required for muscle relaxation to occur
removal of Ca from sarcoplasm
is ATP needed for muscle relaxation or contraction
relaxation
where is the ATPase binding site
on myosin head
what is the pump to remove Ca from sarcoplams for skel mm relaxation to occur
SERCA the sarcoplasmic and endoplasmic reticulum Ca ATPase
AutoAb are against what in myasthenia gravis
nAChrR
initial mm affected in myasthenia gravis
extraocular mm
bulbar (speech swallowing)
neck
proximal limb muscles
Ach binding to R on motor end plate cause what
opening of ligant gated ion channels
depolarization end plate between Na and K
effect of EPP on adjacent sarcolemma of skel m
V Na Channels open and AP generated
enzyme that degrades Ach in NMJ
acetylcholinesterase
what enzyme synthesizes Ach
choline acetyltransferase
what drives Ach uptake into vesicle
vesicular proton elctrochemical gradient (+ voltage and low pH inside)
Where is Ach made
nerve terminal
what allows for Ach uptake by vescile
ACh- H+ exchanger
in ACh
out H+
endrophonium (tensilon) test
give AChEI and see if improve Sx
why does an ice pack help in myasthenia gravis
inhibits AChE activity
two major clinical forms of myasthenia gravis in eyes
ocular MG: only ocular Sx
general MG: generalized weakness
why does MG attack eyes frist
fewer ACh R in eye muscles
high rate firing in eye motor neurons
lower quantal release ACh per event
+ SCC
EMG increase uppon repeated activation
autoAb found against V Ca Ch
Dx
lambert eaton myasthenic syndrome
paraneoplastic
where does LEMS attack
presynaptic VCaCh
decrease ACh vesicle fusion and exocytosis
Which vesicle protein is a Ca sensor
synpatotagmin
conotoxin is from what
marine cone snail
how does conotoxin work
blocks N type VCa ch
analgesic
botulism affects what in NMJ
impaired ACh vesicle fusion
what other toxin (not botulinum) blocks the ACh release
tetanus toxin
why does botulinum toxicity take a while to reverse after given anti toxin
need synaptobrevin (v SNARE) and sNAP 25 (t SNARE) to be newly synthesized
which botulinum attack SNAP 25
A and E
which botulinum attack synaptobrevin
B D F G
what causes spastic paralysis seen in tetanus
central effects bind NMJ presynaptic membrane and retroaxonally transported to SC
NT release is blocked
impact spinal INHIBITORY interneurons
what type of paralysis does botulinum toxin cause
flaccid
RMP
-70mV
what medications promote cellular uptake of K
epinephrine, insulinm, aldosterone
cell death can result in what metabolic state
hyperkalemia
what occurs to membrane with highger K efflux
hyperpolarization
what occurs with a decrease in ECF K
more K efflux, hypokalemia
what occurs with an increase in ECF K
dec K efflux, hyperkalmia
membrane potential less negative aka depolarized
RMP most sensitive to what ion [ ]
K
When is K permeability the highest
relative refractory period of Na channels
methods of removal of NT from synaptic cleft
enzymatic breakdown, cellular uptake, diffusion
NMJ are excitatory/inhbitory or both
always excitatory EPP
how is inhibition of skel mm achieved
CNS through IPSPs at dendrites and cell body of motor neuron
what are the active zones of NMJ
dense spots where synaptic vesicles are clustered
oriented over postjunctional folds
what are postjunctional folds
extensive invaginations on postsynaptic membranes under nerve terminal
increase SA of muscle plasma membrane
what is time delay in impulse transmission with Ach diffusion
50 nm
What is synaptotagmin
Ca R of synaptic vesicles
detect rise in Ca and trigger exocytosis of docked vesicles
synaptobrevin forms a complx with what
SNAP 25 and syntaxin
botulinum toxin C1 blocks what
cleaves syntaxin
what are sarcomeres
actin and myosin units
Z line to Z line
What is the A band
myosin (thick filament)
What is the H zone
middle of A band (part where does not overlap with thin actin)
what is the M line
center of A band
what is the I band
part of ACtin not overlapping with myosin
what is the Z line
thin filament attachment
what is a thick filament
2 myosin heavy chains and 4 light chains
what are the regions of the myosin heavy chains
rod (tail)
hinge (arm)
head (cross bridges)
what are the 4 light chains in thick filament
2 alkali (essential) 2 regulatory
What are the binding sites on myosine heavy chains
actin binding site for cross bridge formation
myosin ATPase site for hydrolyzing ATP
What is F actin
filamentous- backbone
double stranded alpha helical polymer of actin molecules
what are the actin binding proteins
tropomyosin
troponin
tropomyosin blocks what at rest
myosin binding site on actin
tropomyosin interacts with how many actin monomers
7
tropinin interacts with what
1 tropomyosin molecule and actin
torponin T
binds single tropomyosin molecule
troponin C
binds Ca
troponin I
binds actin and inhibits contraction
what happens when Ca binds troponin
tropomysoin slips away from blocking position allowing for cross bridging to occur
how do AP propagate from sarcolemma to interior of muscle fibers
transverse tubules
What is the triad in skel mm propagation
SR cisternae on 2 sides of T tubule that allow for propagation of AP
Channels needed to propagate AP
DHPR- t tubule
RYR- SR
DHPR are found in clusters of how man
4 needed for conformational change allowing Ca release
do you need Ca release to activate RYR
no, mechanical from DHPR
high Ca in SR causes what
inhibits activity of SERCA
what delay inhibition of Ca pump activity
Ca binding proteins in SR lumen (increase Ca amount in SR)
what are the Ca binding proteins in SR
calsequestrin
localized in SR at triad junction
complexes with RYR
what is calreticulin
Ca binding protein in smooth muscle