Excitation Contraction Coupling Flashcards
Somatic motor neurons (what are they and where do their cell bodies sit?)
Voluntary or reflex control
Efferent neurons
cell bodies sit in the CNS (ventral horn of spinal cord)
how many motor neurons is 1 myofiber supplied by?
1
how many muscle cells doe s1 motor neuron axon innervate
a few or many individual muscle cells
what is a motor unit
1 motor neuron and all the muscle fibers it innervates
NMJ (neuromuscular junction)
specialized synapse between motor neuron and skeletal muscle fiber
what are the similarities between a synapse and a neuromuscular junction?
two excitable cells separated by a narrow cleft that prevents direct electrical activity between them
means of communication is via chemical messengers that are released by the Ca 2+ induced exocytosis of storage vesicles when AP reaches the terminal
via the crossing of a neurotransmitter, and binding of it, induces opening of specific channels in the membrane, permitting ionic movements that result in a graded potential (subthreshold changes in membrane potential)
what are the differences between a synapse vs. neuromuscular junction?
synapse is between two neurons and NMJ exist between a motor neuron and a skeletal muscle
whenever you have an AP at a motor neuron you will get an AP of the muscle fiber (one-to-one transmission) WHEREAS one AP is a presynaptic neuron cannot by itself bring about an AP in a postsynaptic neuron ONLY can have AP when summation of EPSP’s brings the membrane to threshold
A NMJ is ALWAYS excitatory VS. synapse which can be both excitatory or inhibitory
what is an active zone ?
dense spots over which synaptic vesicles are clustered (located right over secondary postsynaptic clefts between adjacent postjunctional folds)
waiting to release neurotransmitter
what are postjunctional folds?
extensive invaginations on postsynaptic membrane directly under nerve terminal (high concentration of receptors)
increases surface area of muscle plasma membrane
what is acetylcholinesterase
AChE high concentration associated with synaptic basal lamina (basement membrane)
TERMINATES SYNAPTIC TRANSMISSION after AP
hydrolyzes ACh–> choline and acetate
nicotinic acetylcholine receptors??
these are the receptors that are expressed in high density at crests of postjunctional folds
this is the receptor we will be dealing with in skeletal muscles
where are NT vesicles produced and how do they get to their destination?
motor neuron cell bodies in the spinal cord produce NT vesicles
fast axonal transport translocates vesicles to nerve terminal (microtubule-mediated process)
Vesicles for ACh travel down axon EMPTY but contain presynthesozed peptides/peptide precursors already inside
what does choline acetyltransferase do?
synthesizes ACh from choline and acetyl CoA
what is synaptobrevin?
aka V-snare
essential for transmitter release
forms complex with SNAP-25 and syntax in
helps drive vesicle fusion
what are SNAP-25 and syntaxin
presynaptic membrane proteins t-SNARES
located on the presynaptic membrane of nerve terminal
what is synaptotagmin
Ca2+ receptor of synaptic vesicles
this detects the rise in Ca2+ and triggers exocytosis of docked vesicles
what makes calcium come into the nerve terminal?
at the nerve terminal there are voltage gated calcium channels that respond to action potentials that have reached the nerve terminal
steps in vesicle fusion?
synaptobrevin coils around free ends of syntax in/snap25 and brings the vesicle closer to the presynaptic membrane
when Ca2+ influx comes in, synaptotagmin detects this
this triggers vesicle fusion and exocytosis
what do neurotoxins do? and what is their effect
interrupt process of ACh release by blocking the fusion of synaptic vesicles (b/c of their effects on t-snares and v-snares)
which leads to no signal being transmitted!
Tetanus toxin and Botulinum toxins B,D,F and G do what?
these are endoproteinases (neurotoxins) that digest synaptobrevin
what does botulinum toxins A and E do?
cleave SNAP-25
what does botulinum toxin C1 do?
cleaves syntaxin
what type of receptor is the acetylcholine receptor?
Ionotropic, nicotinic AChR channel
nonselective cation channel at motor neuron endplate
what is the ACh receptor permeable and NOT permeable to?
permeable to cations (Na, K, and Ca) (not specific)
(note current of Ca is small under physiological conditions and its contribution can be ignored)
NOT permeable to anions (Cl-)
WEAK ionic selectivity–> function is to raise Vm above threshold
what happens when Ach binds to its receptor?
graded potential
opening of AChR channel at the muscle end plate does what?
now have increased permeability to Na and K
result is increase in the normally low permeability of Na relative to K+ (because Na usually doesn’t contribute to the resting membrane potential)
Vm shifts to a value between Ek and ENa
End-Plate Potential
what is End-Plate potential
a type of GRADED POTENTIAL which is a decremental spread of current
is is produced by transient opening of AChR
it is an EPSP (increased Na+ conductance drives Vm of end-plate region more positive)
what are the normal physiological conditions of ACh and EndPlate potentials?
presynaptic motor nerve axon AP–> depolarizing postsynaptic EPP
EPP is approximately 40 mV more positive than resting Vm
how is the Neurotransmitter action removed?
AChe hydrolyzes ACh to choline and acetate
removes ACh from NMJ synaptic cleft
Review of events at NMJ
see your drawing
what is a myofibril?
contractile element
contains thick and thin filaments
what is the level of coupling and contraction?
it is at the level of the myofibril and its striations
actin/myosin
Sarcomere
Z line to Z line
what is the A band
myosin thick filaments overlap with actin
what is the h zone
middle of the a band part of myosin where actin does not overlap
what is the m line
extends vertically down center of A band
what is the I band
part of actin not overlapping myosin (does not project into A band)
what is the z line
thin filament attachment
what parts of the sarcomere shorten during contraction?
H zone
I band
Sarcomere is shorter
what are the thick filaments?
bipolar assembly of multiple myosin molecules
2 myosin heavy chains (MHC)
-each heavy chain has a Rod, Hinge and Head
2 alkali light chains
2 regulatory light chains
what are the 2 important binding sites on the head of the myosin heavy chain?
Actin binding site (for cross bridge formation)
Myosin ATPase site (for binding and hydrolyzing ATP)
each head of myosin heavy chains forms a complex with what?
2 light chains (1 alkali and 1 regulatory)
alkali light chain does what?
essential role in stabilizing the myosin head region
what does the regulatory light chain do?
regulates myosin ATPase activity
F-actin?
backbone of the thin filament
it is double stranded polymer of actin molecules
associated with Tropomyosin and Troponin
what are troponin and myosin
2 important regulatory actin binding proteins
what is the important binding site of Actin?
myosin binding site
what blocks the myosin binding site on actin at rest?
tropomyosin
what does troponin interact with?
1 tropomyosin molecule and actin
what does tropomyosin interact with?
7 actin monomers
3 components of Troponin
T
C
I
Troponin T function
binds to a single tropomyosin molecule
troponin C function
binds to Ca
troponin I function
binds to actin and inhibits contraction
titin does what?
tethered from M line to Z line
contributing to force transmission
involved in elastic behavior of muscle by maintaining the resting length of muscle during relaxation (passive stiffness)
what is excitation-contraction coupling ?
process by which electrical excitation of the surface membrane triggers an increase of Ca2+
what do AP’s propagate along?
from sarcolemma to the interior of muscle fibers along the transverse tubule network! Transverse t-tubules
what does a depolarization of the sarcolemmal membrane result in?
rise in Ca2+ inside cell
what is the location of the T-tubules in relation to the muscle fiber?
extend into the muscle fiber and surround the myofibrils at the junctions of the A and I bands
where does intracellular calcium come from?
the sarcoplasmic reticulum
what is the triad
T-tubule membrane and its 2 associated cisternae (specialized regions of sarcoplasmic reticulum)
propagation of AP into T-tubules depolarizes triad
results in Ca release from lateral sacs of the SR
what is the function of the Dihydropyridine receptor?
DHP is a voltage gated channel located on the t=tubule membrane
it is the L-type Ca 2 channel
it induces a conformational change in the Ca release channel (RyR) by mechanical activation
what is the RyR receptor
it is the Ca release channel located on the SR membrane that is facing the T-tuble
releases stored Ca from the SR
what does the release of Ca into the muscle fiber do?
triggers contraction by removing inhibition of cross-bridge cycling
NOTE Ca does not directly interact with contractile proteins, but rather it’s role in contraction is through binding regulatory proteins
in the presence of Ca what does troponin do?
removes tropomyosin from the myosin binding sites on actin
what does mATPase do?
hydrolyzes ATP to ADP and Pi
creating potential energy
what position are myosin head in at rest?
in the cocked position with stored potential energy
what does the interaction between myosin and actin do
pulls the trigger using the stored potential energy
allows myosin to pull the actin toward the center of the sarcomere (power stroke)
sarcomere shortens
Pi is released from the cross bridge to trigger the power stroke
when is ADP release
with the power stroke completion
what must be present for multiple cross -bridge cycling to occur ?
ATP and Ca
what are the steps in the cross bridge cycle?
1= atp binds to myosin head, causing the dissociation of the actin-myosin complex
2= atp is hydrolyzed causing myosin heads to return to their resting conformation
3-= a cross bridge forms and the myosin head binds to a new position on actin
4= pi is released, myosin heads change conformation resulting in the POWER STROKE
the filaments slide past eachother
5- ADP is released after power stroke, and the myosin/actin cross bridge remains in the tightened/shortned position
again ATp binds to the myosin causing dissociation
what is rigor mortis
if their is no fresh ATP available such as after death, then actin and myosin remain bound in rigor complex
what does ATP NOT Do
regulate the cross-bridge cycle of actin-myosin interaction
it will generally continue at physiological levles of ATP
what is relaxation
requires reuptake of Ca from sarcoplasm AND ATP in order to dissociated myosin and actin from each other
it is an ACTIVE process (ca 2+ pumps and ATPase binding site on myosin head)
what happens if reuptake is unregulated?
cross bridge cycling would continue until myocyte is depleted of ATP
what happens when Ca 2+ levels inside the muscle cell decrease?
troponin and tropomyosin move back into place and cover myosin-binding site on actin
what is the minor mechanism for Ca 2 removal from the cytoplasm?
Na-Ca2+ exchanger and Ca2+ pump
both extrude Ca+ across sarcolemma
what is the major mechanism for Ca2+ removal from the cytoplasm?
sarcoplasmic and endoplasmic reticulum Ca2+-ATPase (SERCA) -type Ca2+ pump
what inhibits activity of SERCA?
high Ca2+
what is the function of Ca2+ binding proteins
delay inhibition of Ca2+ pump activity
they buffer increased Ca2+ during Ca2+ uptake and can increase the Ca2+ capacity of the SR
sort of take Ca out of the picture
can have up to 50 binding sites per molecule
Calsequestrin
principal binding protein in skeletal muscle
localized in the SR beneath the triad junction
forms a complex with the Ca2+ release channel (RYR)
facilitates muscle relaxation by buffering Ca2+ and unloads its Ca2+ in the vicinity of the Ca2+ release channel to facilitate EC coupling
Calreticulin
Ca2+ binding protein in smooth muscle
look at the summary slides
do it
