Muscles & Movement: Muscles Flashcards
what are muscle cells called?
myocytes
what does it mean that muscle cells (myocetes) are contractile?
they are capable of producing muscle contractions
What forms of life have myocytes?
only animals
what are the 2 contractile elements of myocetes? what are their main functions?
thick and thin filaments
thick: produce contractile force in muscles
thin: acts as a framework to translate actinomyosin activity into force
What are thick filaments of myocetes made of?
~300 myosin II hexamers
What are thin filaments of myocetes made of?
polymers of alpha-actin (an isoform of actin) that have
ends capped by tropomodulin and Cap Z for stabilization
troponin and tropomyosin on surface
What proteins are compose myocyte thin filaments?
alpha-actin polymers
capping proteins: tropomodulin, CapZ
troponin, tropomyosin
Which myosin type is the muscle myosin?
myosin II
How are thick filaments organized?
~150 hexamers of myosin II on the left and ~150 hexamers myosin II on the right but connected by the tails
heads taaaaaaaaaails heads
where the heads are like bouquets
T or F: thick and thin filaments interact together
true
What are the 2 main muscle cell types?
striated
smooth
What determines whether myocetes are striated or smooth?
the arrangement of myosin and actin
What type of muscles are composed of striated muscle cells?
skeletal and cardiac muscles
How are actin and myosin arranged in striated muscle cells?
in parallel to produce a striped/striated appearance
What type of muscles are composed of smooth muscle cells?
ex. arterioles, iris, bronchioles, GI tract
How are actin and myosin arranged in smooth muscle cells?
there is no specific arrangement (not striated)
What are the stripes
How are thin filaments arranged?
arranged in a fixed array, that is 2 F-actin polymers are wrapped around each other in a helical shape
What surrounds both ends of each thick filament?
an array of thin filaments (6)
What is a sarcomere? which muscle cell type has sarcomeres?
the contractile unit of striated muscle which includes a single thick filament with 2 thin filaments on either end
striated muscles
How are sarcomeres arranged within a striated muscle cell? What does this create?
they repeat in parallel and in series = myofibril
What is a myofibril?
the structure that is composed of repeated, serial sarcomeres in striated muscles
How long are sarcomeres?
2 um long
What is the diameter of myocetes in striated muscles?
20 um
What is the diameter of myofibrils in striated muscle cells?
1-2 um
What makes up a striated muscle cell?
multiple myofibrils
What are the major sections of sarcomeres?
Z-disk at either end
A-band
I-band
M-line
What are the major proteins in sarcomeres (aside from actin and myosin in the filaments) specific for maintaining sarcomere structure?
CapZ
Titin
Tropomodulin
Nebulin
What are Z-disks?
protein plates that form the border of each sarcomere by binding to the + end of thin filaments
they are insertion sites for actin thin filaments
What is the function of CapZ in sarcomeres?
CapZ is a capping protein that binds to the + end of the actin filament to stabilize it and prevent growth and shrinkage
What is the A-band of a sarcomere?
Anisotropic band
the thick filament region of the sarcomere that appears darker
What is the I-band?
isotropic band that is narrower than the A band
the region of the sarcomere where thin filaments span a Z-disk but do not overlap with thick filaments
lighter than A band
WHat is the M-line?
the central line (midpoint of the sarcomere) in the sarcomere between the 2 minus ends of thin filaments
where there is only thick filaments (myosin tails only, no heads)
there is no overlap of thick and thin filaments
What filament is present in the A-band?
thick filaments
What filament is present in the I-band?
thin filaments
What filament is present in the M-line?
thick filament myosin tails, no heads
it is the space between 2 thin filament - ends
What does nebulin do? Where is it located in the sarcomere?
nebulin spans the entire length of the thin filament and twists around the the actin filament
it determines the length of the thin filament
What does titin do? where is it located in the sarcomere?
titin binds and anchors the thick filament to the Z-disks of the sarcomere
Why is it important for titin to be compressible?
because for muscles to contract, the distance between the thick filament myosin heads and Z-disks needs to change
What determines the length of the thin filament?
the length of nebulin bound to it
What maintains the 3D organization of thick and thin filaments in sarcomeres?
proteins like nebulin and titin
How many regions of a sarcomere do thick and thin filaments overlap? where are they?
2
A-band and ? I band during contraction?
Describe the 3D structure of a sarcomere in vertebrates
6 thin filaments are arranged in a cylinder around a single thick filament in the center
each of these 6 thin filaments interacts with 3 separate thin filaments
What is the ratio of thick to thin filaments in a vertebrate striated muscle sarcomere?
1 thick: 2 thin
Where is the - end and + end of the actin in the thin filaments in a sarcomere?
the + end is at the Z disk
the - end is at the M-line
Where is the - end and + end of the myosin in the thick filaments in a sarcomere?
the + end is at the Z disk
the - end is at the M-line
What is tropomodulin? Where is it located in the sarcomere?
it stabilizes the actin depolymerization in the thin filaments at the - end
What makes the actino-myosin activity of muscles different than the sliding filament model?
muscles have specifically myosin II and sarcomere organization contributes too
sarcomere structure prevents myosin from drifting away from actin because 6 actin filaments surround a single thick filament and thick filaments are anchored by titin
duty cycle and unitary displacement of myosin II is significantly shorter
T or F: muscle myosin II has the same duty cycle as other myosins - why/why not?
false
there are ~150 myosin heads at each + end of the thick filament
if each one had a duty cycle of 0.5, at any given time, half of the myosins would be attached to actin = a myosin head can’t pull the filament if there’s 50 other myosin heads attached
What is the duty cycle of myosin II? what does this mean?
~0.05
during each cross-bridge cycle, a given myosin head is attached to actin filament 5% of the time
this prevents myosin heads impeding other myosin heads = efficient
How does the unitary displacement of myosin II differ from other myosins? what does this mean?
it’s much shorter 5-15 nm (ie., the step size is smaller)
movement of each myosin head along the filament is much smaller because there’s so many of them
How does the step size of myosin II compare to that of myosin V?
myosin V was ~37 nm, myosin II is ~5-15 nm
What determines the contractile properties of muscle cells?
sarcomeric organization
specifically the amount of overlap between thick and thin filaments
How does the overlap between thick and thin filaments influence the contractile properties of muscle cells?
myosin (in thick filaments) moves along actin (in thin filaments) so the overlap between the 2 is key for movement
thick filament movement results from the cross-bridge cycles which can only occur where myosin heads can interact with the actin on the thin filament
How is the degree of overlap (and therefor amount of force) between thick and thin filaments in muscles measured?
the distance between the Z-disks = the length of the sarcomere
T or F: more overlap of thick and thin filaments = more force of contraction
true
What is the optimal length of sarcomeres in vertebrates to maximize contractile force (ie., the common length of sarcomeres)?
~2 um
What happens to contractile force if a sarcomere is stretched beyond 2 um?
contraction decreases because there’s less overlap between thick and thin filaments so less contact between myosin heads and actin = less movement of myosin along actin
What happens to contractile force if a sarcomere is compressed to less than 2 um?
thin filaments from adjacent Z disks start to overlap and impede the cross-bridge cycle
too compressed, the thick filaments will collide with Z-disks = max contraction
How long is a myofibril within a muscle cell?
the entire length of the muscle cell
How many sarcomeres are in a given myofibril?
it depends on the length of the muscle cell
What is the diameter of a muscle cell?
it depends on the amount of myofibrils arranged side by side
How does a muscle cell grow in length?
by adding more sarcomeres in series to the end of each myofibril
How does a muscle cell grow in diameter?
by adding more myofibrils (by splitting existing ones and growing the 2 halves)
What is the average force generated by a sarcomere?
it is proportional to its cross-sectional area
~10 N per cm^2 or
it contracts 0.5 um with 5pN of force (pikaNewtons)
How can sarcomeric organization differ to allow for optimization of different contraction types?
sarcomeres can be arranged in parallel to generate maximal force
sarcomeres can be arranged in series to generate maximal shortening
if a single sarcomere is 2.5 um long, when it is activated, how much force would it generate? how much would it shorten?
generate 100pN of force
shorten by 0.5 um
the cross-sectional surface area of a single sarcomere is small
if 10 single 2.5 um long sarcomeres are arranged in parallel, when they are activated, how much force would it generate? how much does it shorten?
generate 1000pN of force but only shrink 0.5 um
because collectively, they have 10x the cross-sectional area, they can summate 10x the force
but together they’re the same length (2.5 um) so they would only shrink by the same amount as a single sarcomere = 0.5um
if 10 single 2.5 um long sarcomeres are arranged in series, when they are activated, how much force would it generate? how much does it shorten?
in series, they are 25 um long but because the cross sectional area is equal to only one sarcomere, they only generate 100pN of force
but they shrink 5um because each sarcomere shrinks by 0.5 um (0.5x10)
How can contraction of skeletal muscles be increased?
by either recruiting more alpha-motor neurons to innervate more myofibrils (stronger stimulus) or increasing strength of APs (temporal summation)
What is the mechanism that regulates muscle contraction?
Excitation-Conctraction coupling (EC coupling)
What are the 3 basic components/steps of regulating contraction via EC coupling?
depolarization of sarcolemma (muscle membrane)
intracellular Ca2+ increases
causing troponin-tropomyosin complex to move positions and initiate sliding filament/cross-bridge cycle = muscle contraction
When is actino-myosin activity activated in striated muscles? (ie., what molecule regulates contraction?)
regulated by intracellular levels of calcium
increase of intracellular Ca2+ stimulates actino-myosin activity
Which 2 proteins are involved in signal transduction for regulating muscle contractions? where are these located?
troponin and tropomyosin on the thin filament
What is troponin? what does it do?
trimeric regulatory protein bound to tropomyosin on thin filaments
function: triggered by high intracellular Ca2+ to cause tropomyosin to move out of myosin-binding spots on actin to allow myosin to bind to actin
What is tropomyosin? what does it do?
a double-stranded regulatory protein that spans 7 actin monomers along the thin filament to block myosin from binding to the thin filament when intracellular Ca2+ is low
What are the 3 subunits of troponin?
TnI
TnC
TnT
What is TnC? describe its structure
the troponin subunit that senses and binds Ca2+
it has 4 Ca2+ binding sites, 2 of which are always bound to Ca2+, the other 2 are unbound when intracellular Ca2+ is low
How many Ca2+ binding sites does TnC have? How many Ca2+ ions are bound when intracellular [Ca2+] is low? when it’s high?
4 binding sites
when low, 2 Ca2+ bound
when high, 4 Ca2+ bound
What is TnI?
a troponin subunit that links troponin to actin and Inhibits actino-myosin ATPase activity
TnI = INHIBITS
What is TnT?
troponin subunit that binds tropomyosin
TnT = Tropomyosin
How does the troponin-tropomyosin complex respond to intracellular changes of [Ca2+]?
it acts as a unit and shifts its position on the thin filament
Describe how the troponin-tropomyosin complex is involved in muscle contraction when a muscle is stimulated
a stimulated muscle causes depolarization of muscle membrane and an influx of Ca2+ into the cell
TnC binds Ca2+ to its regulatory sites which causes a conformational change in TnC
TnC binds to TnI which weakens the bond between TnI and actin = troponin moves
TnT-tropomyosin strong bond allows troponin to pull tropomyosin off the myosin-binding sites on actin
myosin can now bind to actin and cause actino-myosin ATPase activity to trigger the cross-bridge cycle
this stops when Ca2+ decreases in the cell and TnC breaks off 2 Ca2+ ions and troponin pushes tropomyosin back over the myosin binding sites on actin
What are the 4 major differences between EC coupling in cardiac and skeletal muscles?
initial cause of depolarization
shape of AP (time needed for change in membrane potential)
propagation of AP along sarcolemma (muscle membrane)
how intracellular Ca2+ stores are released
what is the sarcolemma?
the muscle cell membrane
Why is it challenging to generalize skeletal muscle contractions?
animals have multiple types of skeletal muscles and there’s different ways they can be built for different functions (ie., sarcomere arrangement)
What activates contraction in all striated muscles?
action potentials
What is the resting membrane potential of the sarcolemma?
-70 mV
Where does the signal for skeletal muscle contraction originate?
it’s neurogenic
it comes from motor neurons (nerves)
What is the neuromuscular junction?
the synapse between motor neurons and myofibers of muscle cells
What neurotransmitter is usually released from motor neurons at the neuromuscular junction? what receptors do muscle cells have?
acetylcholine released
nicotinic ACh receptors
Where does the signal for cardiac muscle contraction originate?
it’s myogenic = originates in the muscle
What is the initial cause of depolarization for skeletal sarcolemma?
motor neurons releasing neurotransmitters (ex. ACh) into the neuromuscular junction
What is the initial cause of depolarization for cardiac sarcolemma?
pacemaker cells in the heart muscle spontaneously and rhythmically depolarize the sarcolemma
What are pacemaker cells? How do they effect the resting membrane potential of cardiac muscles?
cells within cardiac muscle that cause spontaneous and rhythmic depolarization of sacolemma
= unstable resting membrane potential
Describe how depolarization occurs in vertebrate skeletal muscles
motor neuron releases ACh into neuromuscular junction
ACh binds to nicotinic ACh receptor on sarcolemma, opening ligand-gated Na+/K+ channel
Na+ influxes into cell = rapid depolarization and Ca2+-voltage gated channels open
Ca2+ influxes into cell
eventually Na+ and Ca2+ channels close, voltage-gated K+ channels open = K+ fluxes out of cell = membrane repolarizes
What type of Ca2+ voltage gated channels are involved in striated muscle contraction?
L-type
How does the shape and length of the AP along a skeletal sarcolemma differ from a cardiac sarcolemma?
skeletal: AP is narrow and very short
= the inactivation time for Na+ and Ca2+ channels is very short (channels close faster) and there’s little overlap with the contraction
cardiac: AP peaks and decreases much slower (broader signal) and overlaps significantly with the length of contraction = inactivation of Na+ and Ca2+ channels is much longer
How do the AP and subsequently caused contraction in skeletal muscles overlap? what does this mean?
there’s significantly less overlap which means the muscle is experiencing temporal summation (frequent APs)
Narrower AP = shorter inactivation of Na+ and Ca2+ channels
How do the AP and subsequently caused contraction in cardiac muscles overlap? what does this mean?
significant overlap between the 2 because AP is much broader
the Na+ and Ca2+ channels are open for much longer (longer inactivation period)
no temporal summation
Why would you not want temporal summation in cardiac muscles?
temporal summation occurs when there’s little or no refractory period and another AP can be triggered right after slight relaxation from the first one = this causes the response to become additive
this would be dangerous for a heart muscle
What are T-tubules?
transverse tubules are modifications/invaginations of the sarcolemma that dive deep into the muscle cell
How do T-tubules and APs interact?
when the sarcolemma depolarizes, the AP travels into the T-tubules along the sarcolemma
What is the purpose of T-tubules?
to increase efficiency of transmitting APs
T or F: all muscles have T-tubules
false
only muscles that need rapid contraction have T-tubules
What type of muscles would have highly developed T-Tubules? Which would have less?
larger, faster twitching skeletal muscles would have more developed
cardiac muscles have less developed T Tubules
What is the sarcoplasmic reticulum (SR)?
intracellular storage of Ca2+ (bound to calsequestrin) surrounding myofibrils of muscle cells
What protein is Ca2+ bound to in SR?
calsequestrin
what are terminal cisternae? what do they do?
the regions of SR that surround t tubules
they increase intracellular storage of Ca2+ (more developed in skeletal muscles)
are terminal cisternae more developed in skeletal or cardiac muscles?
skeletal
skeletal muscles also have more developed SR and T tubules
Where are the t tubules and terminal cisternae in relation to one another?
they’re adjacent
When does excitation end? What begins next?
when the muscle cell membrane is depolarized , then EC coupling begins when excitation triggers contraction
What is the consequence of an AP moving along the sarcolemma of all vertebral striated muscles?
increase of cytoplasmic [Ca2+]
Where does the Ca2+ flux into the muscle cell cytoplasm from?
extracellularly and intracellular stores
What are the major transporters and channels involved in EC coupling? (on the sarcolemma and SR)
Channels on sarcolemma:
- DHPR
transporters on the sarcolemma:
- NaCaX
- Ca2+ ATPase
channels on SR:
- RyR
Transporters:
- SERCA
What is the main Ca2+ channel on the sarcolemma? what type of channel is it? how is it activated? what happens when it’s activated?
DHPR - dihydropyridine receptor
L-type voltage-gated Ca2+ channel that opens with depolarization of sarcolemma to cause influx of Ca2+ from extracellular space
What is the Sodium-Calcium exchanger? What is its function?
the NaCaX - a reversible transporter on the sarcolemma that exchanges Na+ for Ca2+
function: allows Ca2+ into a cell or brings it out depending on the membrane potential
What is the Ca2+ ATPase?
an active transporter on the sarcolemma that outfluxes Ca2+ from the cell when cell is relaxed (resting MP)
What is RyR? what is its function?
the Ca2+ channel on the SR
functions to release intracellular stores of Ca2+ from the SR into the sarcoplasm
What is SERCA? what is its function?
A Ca2+ ATPase transporter on the SR that pumps Ca2+ from the sarcoplasm back into the SR
What is the purpose of Ca2+ channels in muscle cells?
to increase cytosolic [Ca2+]
L-type voltage gated Ca2+ channels on the sarcolemma (DHPR) increase the flow of extracellular Ca2+ into the sarcoplasm to increase sarcoplasmic Ca2+
RyR channels on the SR release intracellular stores of Ca2+ into the sarcoplasm to increase [Ca2+]
What is the main purpose of transporters in muscle cells?
to reduce sarcoplasmic [Ca2+]
on sarcolemma:
- NaCaX and Ca2+ ATPase can pump Ca2+ out of the cell and intro extracellular space
on SR:
- SERCA (Ca2+ ATPase) pumps Ca2+ from sarcoplasm into the SR
When are channels bringing in Ca2+ into the sarcoplasm open and active?
during sarcolemma depolarization
What happens to the [Ca2+] when the muscle cells relax?
repolarization of sarcolemma triggers Ca2+ to be pumped out of the sarcoplasm
SERCA on SR bring cytoplasmic Ca2+ back into SR, and Ca2+ ATPase on sarcolemma pumps Ca2+ out of cell, NaCaX exchanges intracellular Ca2+ for extracellular Na+
What protein can be used to bind free Ca2+ in the cytosol?
Parvalbumin has Ca2+ binding sites
What happens when [Ca2+ ] decreases in the cytosol?
Ca2+ levels are decreased and the 2 weakly binding Ca2+ sites on TnC of troponin dissociate causing troponin to move and pull tropomyosin back over the myosin-binding sites on actin = muscle relaxation
- excitation = membrane depolarizes = DHPR opens and Ca2+ increases in cytosol
- RyR opens
what type of contractions occur in smooth muscles?
slow and prolonged
Where are smooth muscles usually located?
along the walls of ‘tubes’ in the body like the GI tract, blood vessels, intestines, airways
What are 4 major differences between structure and function of striated and smooth muscles?
smooth:
- no sarcomeres = no orderly arrangement of thick and thin filaments (myosin and actin)
no t-tubules, minimal SR
connected by gap junctions
function as one unit and can contract in all dimensions
What are the main structural components of smooth muscles? how are they distributed?
plasma membrane
adhesion plaques
thin filaments
thick filaments
dense body
microfilaments
adhesion plaques anchor thin filaments to membrane
dense bodies anchor thin filaments to microfilament (cytoskeletal component)
thick filaments overlap between thin filaments
What do both smooth muscle and cardiac cells have in common, but skeletal muscle cells lack?
gap junctions
How do gap junctions affect contraction in smooth muscles?
gap junctions cause the entire muscle to act in unison so contraction occurs throughout the entire muscle at the same time
What is a difference in the direction of contraction between skeletal muscle cells and smooth muscle cells?
skeletal muscle cells contract laterally (remember a single sarcomere loses length, not height)
a smooth muscle cell can contract in all dimensions because gap junctions
What do adhesion plaques do in smooth muscle cells?
attach thin filaments to plasma membrane
What do dense bodies do in smooth muscle cells?
attach thin filaments to cytoskeletal element, microfilaments
T or F: smooth muscles use the same EC coupling mechanism as striated
false
What are 9 major differences between the mechanism of contracting muscles in smooth v. skeletal?
- EC coupling mechanism different
- smooth AP may or may not be involved (always involved in skeletal)
- smooth cells may be connected by gap junctions
- smooth controlled by hormones, nerves, or stretch
- smooth may use RyR or IP3 receptors
- smooth lacks troponin and instead uses Caldesmon containing calmodulin to bind Ca2+
- Caldesmon moves tropomyosin out of myosin-binding sites on actin
what molecule do smooth muscle cells use to bind ca2+ and move tropomyosin out of myosin-binding sites on actin INSTEAD of troponin?
caldesmon
What are 3 types of skeletal muscle fibers?
type I = slow-twitch fibers
type IIa = fast-twitch fibers
type IIb = fast-twitch fibers
Describe type I skeletal muscle fibers
slow-twitch fibers that produce less power and slow velocity
fatigue resistant
oxidative
red (myoblobin)
Describe type IIa skeletal muscle fibers
fast-twitch oxidative red muscle (myoglobin) fibers that generate lots of power and velocity
resistant to fatigue
Describe type IIb skeletal muscle fibers
fast-twitch glycolytic, white muscle (low myoglobin) fibers that produce high power and velocity but not resistant to fatigue
What are the main differences between type IIa and type IIb skeletal muscle fibers?
type IIa is oxidative, red muscle (myoglobin), and resistant to fatigue
type IIb is glycolytic, white (low myoglobin), and can fatigue
Why would there be a diversity in muscle fiber fatigue-ness and force generation?
because animals have a variety of behaviours that require different motor outputs for different periods of time or strengths
What type of muscle fibers would be used for jumping and galloping? why?
fast and high force generation, but fatigable = type IIb
short bursts of energy
What type of muscle fibers would be used for running and walking? why?
fast and high force generation, but fatigue resistant = ongoing need of energy input to maintain prolonged muscle use
type IIa
What type of muscle fibers would be used for standing? why?
slow, fatigue resistant fibers = type I
standing requires longevity, but not high force or speed
What is an example of a fast-twitch muscle fiber that would be needed for jumping and running?
Gastrocnemius
What is an example of a slow-twitch muscle fiber that would be needed for standing, balancing, or walking?
Soleus
How are red and white muscle fibers used differently in fish? why?
red muscles are oxidative and are used for slower swimming speeds (fatigue-resistance, good for maintaining prolonged used of muscles)
white muscles are glycolytic and used for faster swimming speeds (fatigable, good for short bursts of muscle use)
What generates a post-synaptic AP in skeletal muscle cells at the neuromuscular junction?
Cholinergic motor neurons release ACh into the synapse and post-synaptic nicotinic ACh receptors bind it causing an excitatory end plate potential (EPP) which causes an AP
What is EPP?
excitatory end plate potential caused by ACh release in neuromuscular junction and causes AP which causes contraction
T or F: all muscles produce APs to generate contraction
false
In animals that do not produce APs to generate muscle contraction, what neurotransmitters are released at the synapse between motor neurons and the muscle cells?
glutamate
GABA
In animals that do produce APs to generate muscle contraction, what neurotransmitters are released at the synapse between motor neurons and the muscle cells?
ACh (sometimes GABA)
In spiking muscles (ex. in crayfish tail flipping), are APs generated?
yes for the short burst of muscle contraction = twitches
In non-spiking muscles (ex. in crayfish movement other than tail flipping), are APs used? what neurotransmitters are involved?
no, smooth graded contractions are generated rather than twitches by temporal summation or facilitation
GABA and glutamate
How do myosin light chain kinases (MLCK) affect contractions in smooth muscle cells?
MLCK phosphorylates regulatory light chains of myosin to increase actino-myosin ATPase activity and generate contraction
