MSK 14 - Skeletal muscle 1 Flashcards
what are the 4 roles of skeletal muscle
produce force and movement necessary for life
provide support
produce heat
regulate glucose homeostasis
what is the morphological classification of muscles - based on structure
striated = skeletal and cardiac muscle
non striated = smooth muscle
is skeletal muscle voluntary or involuntary movements
voluntary
what happens at the neuromuscular junction in terms of AP and what does it cause
nerve action potential arrives via alpha motor neuron to the neuromuscular junction and AP spreads along fibres leading to excitation contraction coupling
what happens in excitation contraction coupling in terms of Ca2+
calcium has to be released very quickly to floor the cytosol in order to enable contractive filaments to be activated by cross bridge cycle and force production
what are the 2 myofilament proteins found in a sarcomere
myosin and actin
what is a muscle cell called
myofibre
what is the smallest unit of a muscle
myofibres
what is wrapped around the myofibre
endomysium
what is beneath the endomysium
plasma membrane - sarcolemma
what is a bundle of myofibres called in a muscle
fascicles
what is wrapped around a fascicle
perimysium
what wraps around a bundle of fascicles
epimysium - outer connective tissue
what is the structure of skeletal muscle fibres in terms of innervation, branched/unbranched and shape
innervated via neural networks
unbranched long cylindrical (varying lengths)
how are skeletal muscle fibres arranged relative to one another and where are they connected to one another
stacked side by side but not connected to one another apart from at the ends of the muscles fibres to the tendon
why are skeletal muscles multinucleated
during formation of skeletal muscle cells precursor myoblasts that each have a nucleus and fuse together to form muscle fibre
do myofibres have connections to other myofibres
no
describe T tubules in terms of what they are, their orientation and what they do
T tubules are extensions of the sarcolemma which can be transverse or longitudinal
APs propagate along surface of sarcolemma and down the T tubules which activates contraction and synchronises activation
what does the sarcoplasmic reticulum do
store calcium ions
what does calcium ions do
triggers cross bridge cycle
what is a myofibril a bundle of
a bundle of contractile proteins
what is the A band of the myofibril made up of and what is its appearance
is it isotropic/anisotropic
made up of myosin filaments (dark/thick)
anisotropic
what is the I band of the myofibril made up of and what is its appearance
is it isotropic/anisotropic
thin actin filaments
isotropic
what holds the I band in position on a myofibril
Z disc
what does the Z disc hold in position
the I band
where is the M line in a myofibril and what does it do
middle of the H zone
gives contractile proteins structure
what is a sarcomere where are its borders
one contractile unit of myofibiril
from z disc to z disc
what are the junctional areas of the sarcoplasmic reticulum near the T tubules called
terminal cisterna
what is the name of the structure of the 2 terminal cisternae and the T tubule
triad
where are T tubules located in relation to the myofibril zones
at the junction of overlap between the A and I bands
what is calsequestrin and what does it do
protein within the sarcoplasmic reticulum that binds the Ca2+ (can bind aorund 40 Ca2+ per protein)
what receptors does calsequestrin link to and what does this do
links to ryanodine receptors that are release channels from the SR
what does the triad allow
the very small gap between the T tubule and terminal cisternae allows AP excitation to be transferred to the Ca2+ release channels (Ryanodine receptors) at the SR junctional regions
what are the 4 sarcomeric proteins that are associated with the thin actin filaments
titin
troponin
nebulin
tropomyosin
what does titin do
holds the filamentous actin (F actin) in place and connects Z disc to thick filaments/myosin
acts as spring because during contractions, Z disc moves closer to one another so titin protein coils up and holds thick filaments in position
what structures does the titin protein connect
Z discs and thick/myosin filaments
thin actin filaments are held together where at each end of the sarcomere
at the Z disc
what does the hinge region of the myosin filament allow
allows movement of the head by 45 degrees and causes Z discs to move closer together
what do the myosin heads contain
contains ATPase and binding sites for actin/thin filaments
how many heads are on each myosin filament
2
what is the actin chain made up of
globular G-actin molecules
what structures on actin contain the myosin binding sites
troponin
what is troponin
troponin C is on the actin filaments and contains the myosin binding sites
what holds the G-actin molecules together
nebulin
what does nebulin do
holds the G-actin molecules together
what does tropomyosin do
covers myosin binding sites on actin filaments
what covers myosin binding sites on actin filaments
tropomyosin
what happens to tropomyosin at rest
at rest there is a low Ca2+ concentration so tropomyosin blocks the myosin binding sites on actin and so stops force production when youre at rest
what happens to troponin C when there is Ca2+ bound to it
there is movement of troponin I and troponin T which moves aside tropomyosin and exposes the myosin binding sites on actin
what band does myosin form
A band
what is the orientation of myosin filaments in terms of their tail and head
what does this mean for the different zones of a myofibiril
tail faces into the M line, repeated staggered array of heads
so H zone has no myosin heads = no cross bridge possible in that area
what is the actin filament composed of
composed of globular (G) actin molecules linked to two strands twisted into a helix to form filamentous (F) actin
is actin held at fixed lengths
yes by proteins
what band does actin filaments make up
I bands
how are tropomyosin orientated relative to the F actin
rod shaped Tm lies along each F actin in a groove
what other proteins is tropomyosin associated with and what do they comprise
3 proteins
TnT, TnC, TnI
comprises the troponin complex
of TnT, TnC, TnI where does Ca2+ bind
on TnC
what does nebulin do to help the F actin filaments
aligns twisted F actin filaments
in the troponin complex what does TnT do
Troponin tropomyosin
positions the complex on the tropomyosin molecule and holds tropomyosin in place
in the troponin complex what does TnC do
troponin calcium
contains the Ca2+ binding sites
how many Ca2+ binding sites are there on TnC and what is the affinity strength
up to 4 Ca2+ binding sites for each TnC - some are high affinity some are low affinity
in the troponin complex what does TnI do
troponin inhibitor
binds actin and inhibits the myosin head from binding to the actin binding site when cytosolic Ca2+ is low
what two components make up the Ca2+ sensitive switch
Tn complex (TnC, TnT, TnI) and Tropomyosin
what does the Tn complex and Tm create
the Ca2+ sensitive switch
what happens when Ca2+ is high and bound to TnC binding site
what needs to be present for binding to continue
it moves tropomyosin and starts the cross bridge cycle
as long as there is ATP then all myosin heads wants to bind to myosin binding site
the ability of a muscle fibre to develop force depends on what
the interaction of contractile proteins actin and myosin
myosin has a high affinity for actin binding site when what is bound
when ADP.P is bound
when myosin is bound with ADP.P what effect does this have on the affinity for actin binding site
increases affinity
in the relaxed state what orientation are the myosin heads in and what is the binding site like
myosin heads at 90 degrees
tropomyosin blocks the binding site from myosin head
describe the sequence of events of how a muscle shortens due to actin and myosin in the cross bridge cycle
Ca2+ levels increase in cytosol
Ca2+ binds to troponin
troponin-Ca2+ complex pulls tropomyosin away from actin myosin binding site
myosin binds strongly to actin and completes power stroke - swing of myosin head brings Z discs closer together in sarcomere
actin filament moves and muscle shortens
describe the release of myosin from the myosin actin binding site and how this happens - 5 steps
ATP binds to myosin and myosin head dissociates from actin
ATPase of myosin head hydrolyses ATP to ADP and Pi, myosin head remains bound
myosin head swings over and binds to new actin molecule at 90 degrees (relaxed state)
release of Pi initiates power stroke, myosin head rotates and filaments slide
end of power stroke myosin releases ADP and remains in rigor
process repeats
what happens if there is no ATP and the end of the cross bridge cycle
what is this state called
myosin head remains tightly bound to actin - rigor state
what are the 2 roles of ATP in the cross bridge cycle
ATP binding to myosin breaks link between actin and myosin allowing cycle to repeat
ATP hydrolysis provides energy from movement and force development in the cross bridge cycle
when does relaxation come about for a muscle
when Ca2+ concentration in cytosol decreases
how is Ca2+ taken back up and where does it go
taken back up into longitudinal sarcoplasmic reticulum membrane by ATPase (calcium pump)
once back in SR, Ca2+ binds to calsequestrin
when at rest and cytosolic Ca2+ levels are low, what inhibits cross bridge cycle
thin filament proteins troponin (TnC, TnI, TnT) and tropomyosin
cross bridge cycling occurs and generates force as long as what two conditions are met
as long as Ca2+ remains high and ATP is present
what structure hangs in the space between the T tubule and the junctional SR at the triad
the extracellular portion of the ryanodine receptor (electron dense feet region of ryanodine receptor)
what do the ryanodine receptors do
link proteins in T tubule membrane dihydropyridine receptor (DHPR)
how does the DHPR and ryanodine receptors interact
Ap down the T tubule depolarises the membrane around the DHPR and causes an interaction between the feet regions of the ryanodine recpetors and DHPR
opens the ryanodine receptors
what type of receptor is the DHPR
voltage gated Ca2+ channels in sarcolemma
are DHPRs functional Ca2+ channels in skeletal muscle why
no
because there is no effective transfer of Ca2+ across the T tubule membrane
what are ryanodine receptors (RyR)
Ca2+ release channels of SR
what does it mean when we say that troponin C binds up to 4 Ca2+ cooperatively
when one or 2 sites bind Ca2+, the other sites bind Ca2+ more easily
how many high affinity and low affinity binding sites are there on troponin C
2 high affinity
2 low affinity
what type of RyR is in skeletal muscle
RyR1
where do the RyRs exist
at the terminal cisternae of junctional SR
what inhibits skeletal RyR activation
cytosolic Mg2+
how does voltage sensor DHPR activation overcomes Mg2+ inhibition
sense depolarisation of membrane around DHPR and causes them to interact with RyR and opens them
what overcomes the Mg2+ inhibition of RyR
DHPR activation
what are the benefits of voltage dependent excitation contraction coupling - 4 reasons
rapid response
doesnt depend on sarcolemal membrane channels opening and current flow
no reliance on sarcolemme diffusion
muscle contraction can occur in abscence of extracellular Ca2+
