WEEK 5 Flashcards
the primary function of muscle is to convert ______ into ______
energy (liberated by ATP Hydrolysis) ; mechanical work
the ability for muscle to shorten allows for what secondary functions?
- maintain and regulate body posture and position
- respiration
- heat generation
- communication
- constriction of organs and blood vessels
- pumping blood
what are the general properties of muscle
- excitability
- contractibility (the ability to forcefully shorten)
- extensibility ( aka distensibility- the ability to stretch
- elasticity ( the ability to recoil)
what is the mode of control for skeletal, cardiac, and viscera muscle
skeletal: voluntary
cardiac + viscera: involuntary
what is the histology of skeletal, cardiac, and viscera muscle
skeletal and cardiac: striated
viscera: smooth
what are the three connective tissues found in skeletal muscle? and what do they surround?
Epimysium: surrounds muscle
Perimysium: surrounds bundles of muscle fibers called fascicles
Endomysium: surrounds individual muscle fibers
the endoplasmic reticulum is to a regular cell as sarcoplasmic reticulum is to a ____
skeletal muscle fiber/cell
the plasma membrane in a muscle fiber is called what? the cytoplasm of a muscle fiber is referred to as what?
sarcolemma; sarcoplasm
what comprises the triad in a muscle fiber
1 transverse tubule and 2 terminal cisterns
what is found within transverse tubule?
extracellular fluid
where does the SR end?
at the terminal cisterns
where does a skeletal muscle fiber store Calcium?
the Sacroplasmic reticulum
what comprises the sarcomere in a skeletal muscle
- sacromere is defined by Z-lines
- they are arranged longitudinally
- includes the M-line (in the middle)
- A-band and I-bands flanked on either side
- an H-band longitudinally within the A-band
where do actin filaments anchor? and what do they anchor to?
- at the Z-line and extend to the m-line
- actin filaments specifically anchor to alpha-actinin
what do myosin filaments anchor to
myosin proteins anchor to the m-line and extend to the z-line
what is the central region of the A-band
H-band
a-band aka ______
anisotropic
what is the darkest band?
A-band
what bisects the I-band
the Z-line
What can be found in the I-band
actin filaments only
What gives the striated pattern in skeletal muscle?
- the actin and myosin arrangements give the stripped appearance
- the striated pattern represents the amount of actin and myosin present as well as amount of overlap
Myofibrils are composed of what?
- Actin (thin filaments)
- myosin (thick filaments)
- accessory or supportive proteins
What proteins in the m-line do myosin proteins anchor to
myomesin
what can be found in the H-band
myosin only
At the darkest region of the A-band?
where the actin and myosin overlap
thick filaments are mostly made of what protein
myosin
Describe class II myosin dimers
Each monomer has 1 heavy chain and 2 light chains.
In the heavy chain :
- globular head (S1)
- motor domain
- ATPase activity
- actin binding domain
- a neck region
- a-helix tail
2 light chains:
- one is essential and one is regulatory
- contains calcium binding proteins
what are the actin-associated proteins?
troponin
tropomyosin
* they are responsible for myosin and actin interactions
Describe tropomyosin
- a long string like polypeptide made of two identical alpha helices
- tropomyosin can hide or expose the “active sites” on each globular actin molecule
- can cover several binding domains at a time
Describe troponin (troponin, troponin C, and troponin I)
- a heterotrimer (3 distinct subunits)
- Troponin (TnT): a binds a single molecule of tropomyosin and helps position it on the F-actin strands
- Troponin C (TnC): binds Calcium. there are two pairs of calcium binding sites.
- Troponin I (TnI): binds to actin and inhibits contractions
describe the 2 pairs of binding sites on Troponin C
- 1 pair is a high affinity binding site. Binds calcium even when there are low levels of Calcium
- 2 pair is a low affinity binding site. Calcium only binds when there are high levels of Calcium in sarcoplasm.
what role does Troponin play in contraction
- TnT binds tropomyosin and TnC, and TnI binds to actin subunits
- when Calcium levels are high and TnC has 2 calcium bound, but low affinity sites don’t the confirmation of troponin and tropomyosin complex obscure the myosin binding site on actin, prohibiting access for the myosin head
- ## when intracellular levels of calcium are so high that low affinity sites bind calcium, it induces a conformational change causing myosin sites to be revealed on actin
what is the function of calcium in the troponin + tropomyosin complex
- it removes the inhibition so that myosin can bind to the actin subunits.
Name and describe the additional proteins that provide structure and stability
Titin
Nebulin
a-actinin
myomesin
Describe Titin protein
- very large (3000 kd)
- a single Titin protein extends from the M-line to the Z-disc
- Titin molecules act like springs (can stretch and recoil)
- they keep the myosin filaments centered in the sarcomere
- maintain the resting tension that allows a muscle to snap back if overextended
describe Nebulin
- Nebulin filaments extend from the Z-disk and are associated with actin
- they regulate the assembly of actin filaments and determines their length
- they make sure that actin filaments don’t over polymerize or under polymerize
What does a-actinin do at the Z-line?
anchors the thin filaments (actin)
What does myomesin do at the m-line?
anchors myosin molecules in place
- myosin projects from m-line towards z-line
describe dystrophin
- flexible, rod-like protein located mostly in the inner leaflet of the sarcolemma
- links the contractile apparatus to the sarcolemma (plasma membrane)
- the N-terminus contains the actin binding complex
- the C-terminus interact with a protein complex associated with the sarcolemma
- associated with Duchenne muscular dystrophy
What is Duchenne muscular dystrophy
- a sex linked disease that affects more boys than girls
- frameshift mutation, results in deletion of exon in dystrophin protein making it non-functional or partially functional
- constant cycle of inflammation, scarring and loss of muscle mass
What is Duchenne muscular dystrophy
- a sex linked disease that affects more boys than girls
- frameshift mutation, results in deletion of exon in dystrophin protein making it non-functional or partially functional
- constant cycle of inflammation, scarring and loss of muscle mass
True or False.
1. muscles are excitable cells
2. skeletal muscle does not rely on neural impulses to be activated
- True
- False. skeletal muscle does rely on neural impulses to be activated
where are the cell bodies of skeletal muscle located
in the ventral horn of spinal cord
skeletal muscle relies upon neural impulses from ________ motor neurons to be activated
somatic
At what synapse are electrical signals sent to activate muscle fibers
- neuromuscular junction
True or False.
A single motor neuron innervates several muscle fibers
True.
- A signal axon innervates 100-200 muscle cells, thus coordinating their contraction
- the axon are also highly myelinated
- the # of muscle fibers innervated by a singular motor neuron is called a motor unit
Describe the motor end plate in skeletal muscle
- lies opposite the presynaptic terminal
- where nAChR (nicotinic acetylcholine receptor) and AChE (acetylcholine esterase) are located
- when post junctional folds are located. These folds increase surface area available for synaptic communication to take place
describe End plate potential
- depolarization of the sarcolemmal potential at the motor end plate
- similar to an EPSP seen in neurons.
- caused by release of acetylcholine
- fail safe mechanism to produce action potential for activation of muscle fibers
describe what happens at the motor end plate in skeletal muscle
- presynaptic terminal depolarizes
- acetylcholine is released
- acetylcholine receptors are type 1 receptors. which are receptive to nicotine, and are inotropic channels
- acetylcholine binds and ion channels open, thus changing permeability of sarcolemma
- acetylcholine esterase breaks down residual acetylcholine into constituent parts to be taken back up and recycled.
skeletal action potentials compared to neural action potentials
- skeletal muscle have a more negative resting membrane potential. Meaning it’s more permeable to potassium at rest
- skeletal muscle propagates action potential quicker. (5 m/sec)
- each skeletal muscle fiber has 1 or 2 motor end plates located near the middle of each fiber
- mass ion flow of Calcium and sodium resulting in rapid depolarization
- Na+ channels inactivate as voltage gated K+ channels open (delayed)
- the potassium channels allow for repolarization of membrane potential
- action potentials in skeletal muscle are twice as long as motor neuron action potentials
- skeletal muscle does not have an afterhyperpolarization phase, neurons do.
- no inhibitory postsynaptic potential on skeletal neurons. inhibition would have to take place at the spinal cord level
Fill in.
The triad is a vital component of ___________ __________ coupling in skeletal muscle
excitation-contraction
describe the role the triad plays in excitation-contraction coupling in skeletal muscle
- the action potential generated at the neuromuscular junction (NMJ) travels down the T-tubules
- T-tubule membranes express dihydropyridine receptors (DHPR). it function as voltage sensors
Describe DHPR and RYR
- skeletal DHPR are very similar to L-type voltage gated Calcium channels found in other tissues
- they do not function as calcium channels in skeletal muscle
- they are voltage sensors in skeletal muscle
- action potential activates DHPR when it depolarizes the membrane.
-DHPR senses the depolarization and undergoes conformational change. - this conformational change opens the Ryanodine receptor (RYR) allowing calcium w/in the sarcoplasmic reticulum to flood into the sarcoplasm
- this elevates intracellular Calcium within the sarcoplasm
- the RYR (calcium channels) are expressed on the terminal cistern
True or False.
Calcium does not regulate actin-myosin interactions in striated muscle.
False.
Calcium does regulate actin-myosin interactions in striated muscle
In striated muscle what regulates the calcium interactions with actin-myosin
the troponin-tropomyosin complex
explain how calcium concentration affects the troponin-tropomyosin complex
- when calcium efflux from the SR elevates intracellular levels high enough so calcium can bind low affinity sites of TnC
- this initiates a series of conformation changes that shifts the tropomyosin-troponin complex to clear the way for myosin-actin to interact
Fill in.
the regulatory proteins inhibit the interaction of actin and myosin in the absence of __________.
calcium
Fill in.
Calcium initiates contraction by __________ the inhibitory effect of the troponin-tropomyosin complex.
reversing
How is the inhibition of the troponin-tropomyosin complex linked to action potential
- action potential elevates intracellular calcium levels that are released from the SR.
- the calcium is able to then binding and inhibit the troponin-tropomyosin complex.
How much does the cross bridge cycle advance the myosin head?
- By 2 actin monomers, about 11 nm
What happens if the ATPase activity of the myosin head in skeletal muscle is inhibited
- the myosin would not be able to cleave the tertiary phosphate
- the myosin would be unable to return to its resting conformation
- contraction would not occur
- the cross-bridge cycle would halt/stop
- the myosin head ATPase activity sets the timer for the cross bridge cycle
describe the cross bridge cycle
- Myosin head starts bound to actin, no ATP is attached. This attached state is responsible for rigor mortis (where no more ATP is produced).
- ATP binds to myosin head, causing the dissociation of the actin-myosin complex.
- ATP bound reduces the affinity of myosin head for actin this is the released state.
- cleaved phosphate remains attached to myosin
- ATP bound activates ATPase activity of globular head. ATPase cleaves tertiary phosphate, cleavage triggers conformational change that allows head to flex
- ATP is then hydrolyzed, causing myosin head to return to resting conformation. This is the cocked state
- myosin head is position opposite the new actin subunit
- myosin head has a higher affinity for actin subunit
- myosin head is position opposite the new actin subunit
- a Crossbridge forms and myosin head binds to a new position on actin.
- Phosphate is then released from myosin, triggering the power stroke, a conformational change that causes the actin filament to be drawn along the myosin.
- this generates force and motion
- ADP is released from myosin completing the cycle.
when there is high Calcium and ATP present what will happen to the cross-bridge cycle?
- Cycle continues
- the result is progressive shortening of muscle.
Fill in.
All muscles contract by the ___________ or sliding of the thick and thin myofilaments
interdigitation
True or false.
In striated muscle, the myofilaments themselves change their length
False. they do not
- In striated muscle shortening is a result of sarcomeres shortening in length because the Z-lines are pulled closer together and the I-band narrows.
Compared to relaxed muscle, in contracting skeletal muscle the H-zone is ________ and the I-zone is ________
reduced; shorter
Compared to relaxed and contracting skeletal muscle, in fully contracted skeletal muscle the H-zone and I-zone is ________. This results in full overlap
not visible
Fill in.
Termination of skeletal muscle contraction requires that ____________ _________ fall to rest
intracellular calcium
Describe how termination of contraction in skeletal muscle occurs.
- Action potential passes, the DHPR-RYR complex closes. This prevents further calcium efflux from the SR.
- acetylcholine esterase cleans up excess calcium at the synaptic cleft.
- Ca-ATPases pump calcium back into the SR
- calcium binding in the SR via calsequestrin. Calcium diffuses from the longitudinal SR to the terminal cisternae where It binds to calsequestrin
- Ca-ATPases and Na-Ca exchangers pump calcium out of the cell. the Ca-ATPase is found on the sarcoplasm and membrane of S. the exchanger is found on the membrane on S.R.
- Cytoplasmic Ca binding proteins calbindin and parvalbumin. They have a higher affinity for calcium than TnC , but binds calcium slowly
- calcium dissociates from TnC and the inhibition of actin and myosin interactions resume. the muscle cell relaxes.
Fill in.
The contraction generated by a single action potential is called a __________ ___________
muscle twitch
What are the three components of a muscle twitch
- latent period
- contraction phase
- relaxation phase
Describe the latent period, the contraction phase, and the relaxation phase
- latent period; the time it takes for action potential to initiate the excitation-contraction coupling
- contraction phase: when the muscle is generating tension
- relaxation phase: the time it takes for the muscle to return to its normal length
Fill in.
the motor neurons that innervate skeletal muscle are called _______ _______ ________.
Alpha motor neurons
Fill in.
A motor unit consists of one alpha motor neuron and the set of _______ _______ innervated by that neuron
muscle fibers
True or false.
Every muscle has its own motor neuron pool
True.
describe a motor neuron pool
the population of alpha motor neurons that provide innervation for that muscle.
- a pool consists of many neurons, each of which innervate a motor unit within the muscle
- the max number of neurons innervating a given muscle. cannot get bigger or smaller
Muscles we have extreme fine control over, such as fingers, have what size motor units
- small
- this allows us to generate very precise movements
small motor units produce _______ control and don’t generate a lot of _______
precise ; force
True or false.
Large motor units produce a lot of fine control, and generate force quickly
false.
large motor units do not produce a lot of fine control, but generate force quickly
True or false.
a motor neuron axons typically branch so that a single axon innervates 100-200 muscle cells
True.
Do muscle units fire asynchronously or synchronously?
asynchronously
random firing of motor units is known as what?
muscle tone
- mediated by sequential activation of different motor units part of a muscle
What happens if the innervation to a skeletal muscle is cut
there will be no muscle tone
- this is known as flaccid paralysis
Fill in.
The sum activity of motor units in skeletal muscle can increase ________
strength
- the sequential activation of motor units results in sustained tension in muscle.
Why is the refractory period in skeletal muscle unique
- unique b/c refractory period allows for temporal summation of tension
- this is one way that force of contraction can be increased.
True or False.
In skeletal muscle, if motor neuron fires action potential before refractory period the muscle can respond
False.
- the muscle can only respond to action potential after the refractory period
describe incomplete tetanus in skeletal muscle (unfused) and complete tetanus (fused)
Incomplete tetanus: Action potential frequency is increased so that muscle is unable to relax back to rest.
Complete tetanus: frequency of action potential is so great that the muscle is able to sustain very high levels of calcium inside the muscle, and it continues to contract. it is undergoing continuous cross bridge cycles.
How can force be graded and regulated in skeletal muscle?
- increasing the frequency of nerve stimulation (increase action potential)
- recruiting more motor units from the motor neuron pool ( more muscle fibers are being innervated to generate more force)
- recruiting alpha motor neurons that innervate a larger set of muscle fibers ( as opposed to motor units that innervate a smaller number of fibers)
When is maximal force generated in skeletal muscle?
- when there maximum recruitment of motor neuron pool nd
When is maximal force generated in skeletal muscle?
- when the maximum recruitment of motor neuron pool is reached and the frequency of action potential is sufficient to reach tetanus
Fill in.
the length of a muscle prior to stimulation is _______
pre-load
Fill in.
pre-load is a fundamental determinant of the amount of ________ that a muscle can develop upon stimulation
force
True or false.
the amount of active force a muscle can generate is related to the number of cross-bridges that can be formed.
true.
this is true for booth smooth and striated muscle.
what is Lo or Lmax
ideal amount of overlap of actin-myosin for producing the number of cross bridge cycles that can be formed.
this is true for striated and smooth muscle too.
Describe ascending limb
- muscle is shortening, so length decreases
- eventually tension plateaus
- when tension plateaus it hits Lo or Lmax
describe descending limb
- muscle elongates, so increases in length after max tension
- eventually there is no overlap of actin and myosin
What is passive tension
- the tension that is produced by muscle without any stimulation
- the proportion of elastic proteins present as opposed to non-elastic proteins/collagen.
describe muscles with more collagen than elastic proteins
- less elastic proteins makes the muscle stiffer
- more collagen present
- there is a dramatic increase in passive tension as stretch is increased. cardiac muscle is very similar to this
describe muscles with more elastic than collagen proteins
- more elastic muscles have less collagen
- tolerate stretch more until the point where elastic proteins are exhausted and tension increases significantly
True or false.
generic skeletal muscle is more elastic than skeletal muscle
True.
What is total force
the sum of passive force and active force
At short muscle preloads, all force is ________
active
at longer lengths there is a greater contribution from ________ force
passive
in skeletal muscle, active tension decreases as sarcomere length _______ . Passive tension increases as sarcomere length __________
increases; increases
what is isometric contraction
- increase in tension but not change in length
- this is when the muscle is generating force, but not doing observable work
- the muscle contracts but there is no change in length
- important in maintaining posture (postural muscles) and stabilizing joint positions
what is isotonic contraction
- tension remains relatively constant, but the muscle changes length.
- when muscle is able to do observable work
- when muscle is generating tension there is no change in muscle length at first.
- the muscle is generating enough force to overcome the weight of the muscle and the object.
- once tension develops and exceeds resistance, the muscle beings to shorten.
- muscles then relaxes, tension decreases, and muscle length increases back to rest.
- types of isotonic contraction include concentric contraction, and eccentric contractions
what are concentric contractions
- a type of isotonic contraction
- when the muscle generates tension and the entire muscle shortens (i.e bicep curl)
what are eccentric contractions
- when the muscle is actively lengthening, in a controlled fashion
- decelerating object
what are the two resistances the muscle has to overcome to contract
- weight of the muscle itself
- weight of object being moved
in skeletal muscle when the tension is generating is there a change in muscle length? what happens as tension is generating?
NO. because the muscle is generating enough force to overcome the weight of the muscle and object.
- at this phase it is experiencing isometric contractions
what are the functions of ATP in muscle?
- ATP binds to myosin causing dissociation from the actin in the cross-bridge cycle, allowing the cycle to then proceed.
- hydrolysis of ATP by myosin energizes the cross bridges , by providing the energy needed to generate force.
- hydrolysis of ATP by the Ca-ATPase in the SR provides the energy required for the active transport of Calcium into the SR ending the contraction
what are the sources of ATP available for muscle?
- cytosolic ATP; in the sarcoplasm. this is immediately available for skeletal muscle but only for a few seconds of activity
- phosphorylation of ADP by creatine phosphate (an anaerobic process)
- glycolysis
- oxidative phosphorylation
Describe creatine phosphate and how it provides ATP for muscles
- creatine phosphate is a high energy molecule
- Phosphocreatine + ADP => Creatine + ATP ; via creatine kinase
- phosphocreatine phosphorylates ADP using creatine kinase.
- creatine kinase is abundantly expressed in m-line of the sarcomere
- ## creatine kinase extends the ATP population in muscle enough to replenish the cytosolic pool several times
What sources of ATP are responsible for sustained ATP activity in the muscles
- glycolysis and oxidative phosphorylation
Where is glycogen stored?
- sarcoplasm of the skeletal muscles
- liver
Describe the flow of glycogen during exercise
- glycogen > G6P > pyruvic acid > lactic acid > blood > lactic acid (liver) > pyruvic acid (liver) > G6P (liver) > glucose (out of liver) > the blood > G6P in skeletal muscle
During intense exercise, when O2 is low, the body relies on what to meet ATP demands
- glycolysis
- glycogen breakdown in liver to supply glucose to muscles in order to support glycolysis
what is the myosin ATPase activity of type I, type II and type IIb muscle fibers? as well as duration of their contractions
type I - slow myosin ATPase ; long contractions
type IIa - fast myosin ATPase ; short contractions
type IIb - fast myosin ATPase ; short contractions
Of Type I, IIa, and IIb which muscle fiber is easily fatiguable?
- type IIb is easily fatiguable
- type I and IIa are resistant
what are the metabolism characteristics of the three different muscle fibers?
- type I: oxidative
- type IIa: BOTH (anaerobic and aerobic)
- type IIb: anaerobic and glycolytic
of type I, IIa, IIb muscle fibers which one has a rich blood supply? also which type is mitochondria dense?
Type I is rich in blood supply. b/c it is high in capillary density
- type IIa is medium capillary density
- type IIb is low in capillary density
Type I is mitochondria dense
which muscle fibers are high in glycogen?
- type IIa and IIb
True of false.
whole muscle is composed of a mix of each muscle fiber type
True.
slow-oxidative fibers, combine low ATPase activity with high oxidative capacity, are what type of muscle fibers
type I
fast-oxidative-glycolytic fibers, combine high myosin ATPase activity with high oxidative capacity, are what type of muscle fibers
type IIa
fast glycolytic fibers, combine high myosin ATPase activity with high glycolytic capacity, are what type of muscle fibers
type IIb
gastrocnemius muscle of the calf contain about half _______ and half ____ type fibers
slow; fast
the deeper calf muscle, the soleus muscle is dominated by ______ twitch fibers , making it _______ to fatigue
slow ; resistant
our extraocular muscle are made of mostly _____ twitch muscle fibers.
fast
cardiac muscle is found exclusively in the ______ where its function is to provide the motive ______ needed to propel the blood throughout the _________
heart ; force ; circulation
cardiac muscle contracts spontaneously in the absence of _______ or ______ input
endocrine ; neural
what are the different cell types in the heart
contractile cardiac muscle cells
- cardiac muscle fibers
- cardiac myocytes
- cardiocytes (force generating)
describe the muscle cells in the heart
- striated, like skeletal muscle
- functions involuntarily
- autorhythmic: meaning it contracts spontaneously without neural or hormonal input. they produce action potential all on their own without neural or hormonal input. this is why the heart needs a conduction system
How does cardiac muscle differ from skeletal muscle
- it has one or two centrally located nuclei
- has branched cells. forms diads not triads
- cells are connected at their ends by junctions called intercalated discs
- has a smaller sarcoplasmic reticulum
- does not have fully developed terminal cistern
what do intercalated discs do?
- they hold adjacent cardiac cells together
- provide strong sites of adhesion
- permit electrical synchronization/ communication
what are the junctions found at the ICD/
- Desmosomal junctions (Ds)
- Adherens junctions (Fa)
- Gap junctions (Gj)
Describe the Cadherins found at the ICD
Cadherins are a superfamily of Calcium dependent cell adhesion molecules concentrated at the cell junctions like adherens junctions, and desmosomes
classic cadherins (anchor actin filaments)
- are found in adherens junctions.
- single pass transmembrane proteins
- bind to cytoplasmic linker proteins called catenins
- catenins then bind to actin filaments of cytoskeleton
Desmosomal cadherins (anchor IF)
- single transmembrane proteins
- bind to intracellular linking proteins that then link to intermediate filaments
electrical continuity between cardiac myocytes is mediated by ________ _______
gap junctions
what are the three different connexin proteins expressed at different cardiac locations? where are they expressed
- Cx43 and Cx40 expressed at the atrial myocardium gap junctions
- Cx43 expressed at the ventricular myocardium gap junctions
- Cx45 exclusively found in the AV node
describe the electrical properties of the different gap junctions
Cx43 and Cx40 have large electrical conductances (60-120ps and 175-210ps)
Cx45 has a small conductance (30-40 ps)
what is thought to be responsible for the slower conduction though the AV
- the expression of Cx45, which has a low conductance
ventricular myocytes have a _______ action potential
long
- it is characterized by a long plateau period
- longer a.p compared to neuron and skeletal muscle
What are the different phases of ventricular myocyte action potential?
Phase 4: the resting phase
- it is dominated by potassium (K+ rectifier). therefore has a very negative resting membrane potential because potassium is leaving
- sodium and calcium channels are closed
- (-90mv)
Phase 0: depolarization
- rapid influx of sodium through open voltage gated channels
- membrane potential increases quickly
phase 1: early repolarization (or notch)
- transient K+ channels open
- K+ efflux returns the membrane potential to 0mv
- at the end of 1 transient K+ channels close
phase 2: the plateau phase
- influx of Calcium through the L-type Calcium channels
- influx of Ca is electrically balanced by K+ efflux through the delayed rectifier channels
- the L-type channels are still open and there is a small constant inward current of Calcium
- the plateau phase lasts as long as the calcium channels are open
Phase 3:
- calcium channels close but delayed rectifier K+ channel remains open
- returns membrane potential to -90mV
Fill in.
L-type channels in the ventricular myocytes are activated _______
slowly
What is responsible for the sustained period of repolarization in phase 2
influx of calcium through L-type channels channel
true or false.
the initial influx of Calcium into myocytes through L-type Calcium channels during phase 2 of the action potential is sufficient to trigger contraction of myofibrils
False it is not enough
- this is where the calcium-induced calcium release comes into play
How does the calcium induced calcium release mechanism help with contraction of cardiac muscle cells?
- the CICR mechanism amplifies this initial calcium influx from the L-type calcium channels in phase 2
- this CICR mechanism is unique to cardiac muscle
- the CICR mechanism helps release the bulk of calcium needed to bind to TnC to induce the contraction
explain how the process of contraction in cardiac muscle
- calcium entering acts on the DHPR, the L-type channel, which acts as a calcium channel not just a voltage sensor
- it is not enough calcium to bind the low affinity TnC, so this is where the CICR mechanism comes into play and releases bulk of Calcium from the S.R
- now calcium can bind low affinity TnC and induce contraction
- cardiac muscle needs extracellular Calcium to contract whereas skeletal muscle does not, and contracts independently of extracellular Calcium
- contraction ends by the pumping of calcium out of the cell and into the SR (Ca-ATPase, Ca-Na exchangers - 1 Ca out and 3 Na in)
What do cardiac glycosides do?
- cardiac glycosides inhibit Na-K pump
- this result in the intracellular accumulation of sodium
Fill in.
Refractory period on cardiac muscle is ________ than in skeletal muscle
longer
because of the prolonged refractory period in cardiac muscle, it is not possible to do what?
sum tension. Making tetanus impossible
- therefore force cannot be regulated in this way
compare passive tension in cardiac muscle and skeletal muscle
- cardiac muscle rises at much shorter sarcomere lengths and rises much more steeply compared to skeletal muscle
- cardiac muscle is less elastic than skeletal muscle
- skeletal muscle has a broader range than cardiac muscle for generating tension
compare active tension in cardiac muscle and skeletal muscle
- the shorter length range for generating tension in cardiac muscle is because of the following:
- the calcium sensitivity of the myofibrils increases with muscle length
- the amount of calcium supplied to the myofibrils through CICR during systole increases with muscle length
in cardiac muscle, small changes in length produce a ______ change in tension . also small changes in preload produces a ____ change in force of contraction generated by cardiac muscle.
large ; large
True or false.
You an recruit more muscle cells to increase force in the heart
False.
the heart is a syncytium
how is force modulated in the cardiac muscle
- modulate calcium availability
- modulate the plateau phase
- change the extracellular calcium concentration (ion concentration gradient) - modulate contractile protein sensitivity to calcium
- prolonging the activity of TnC - modulate the length-tension relationship by shifting the preload to a more optimal starting length
- this will shift the force generated by the heart
True or False.
Smooth muscle is not organized into sarcomeres
True
where is smooth muscle found
- organized into layers or sheets
- it is in hollow organs (stomach), intestines, arteries, veins, and tracts of respiratory system
- in the eyes- it regulates the size of the iris and shape of the lens.
- plays a vital role in the movement of the luminal contents of hollow organs
describe the structure of smooth muscle
- spindle shaped
- single centrally located nucleus
- a lot smaller than skeletal muscle
- produce their own Endomysium
- have dense bodes which are a-actinin
- actin extends off dense bodies (a-actinin) in a radial pattern
- myosin is anchored to actin filaments in the middle. they pull the dense bodies together in a corkscrew fashion, not linearly causing the cells to shorten
- Intermediate filaments link the dense bodies like a mesh
the dense bodies are analogous to _______
Z-discs
dense bodies are anchored to the ________ and are present in the ______
sarcolemma ; sarcoplasm
thick filaments in smooth muscle _______ actin filaments
cross link
true or false.
smooth muscle has T-tubules, but no terminal cistern
False.
smooth muscle has neither t-tubules or terminal cisternae.
True or false.
1. smooth muscle has a large Sarcoplasmic reticulum
2. smooth muscle requires action potentials to shorten
- false. smooth muscle has a small SR.
- they do not require a.p to shorten
what connects smooth muscle cells?
connective tissue
Fill in.
Smooth muscle contraction requires an elevation of intracellular Calcium
True.
What happens in smooth muscle cells once intracellular Calcium is elevated?
- 4 calcium bind reversibly to calmodulin. this forms an activated Ca-Calmodulin complex
- Ca-Calmodulin activates myosin light chain kinase (MLCK). this takes a phosphate off ATP and applies it to light chain on myosin
- MLCK phosphorylates a regulatory light chain on myosin.
- once light chain is phosphorylated the myosin head can bind repeatedly to the actin filament proceeding with the cross-bridge cycle.
- the phosphorylation also activates the myosin head ATPase necessary to support the cross bridge cycle.
- smooth muscle relaxation can only occur once the intracellular calcium drops below a critical level
True or false.
Troponin and Tyrpomyosin complex is present in smooth muscle.
false.
what does myosin phosphatase do
dephosphorylates phosphorylated myosin in smooth muscle
how does contraction terminate in smooth muscle?
- decrease intracellular calcium
- once calcium levels are low calcium is no longer bound to calmodulin
- uses primary and secondary active transporters to transport Calcium into SR or into extracellular
- myosin phosphatase helps with muscle relaxation by removing phosphate from phosphorylated myosin
How is intracellular calcium elevated in smooth muscle?
- voltage gated Calcium channels: electrical gradients
- ligand gated calcium channels; hormone or neurotransmitter
- release of calcium from the SR. this is controlled independently of the entry of calcium from the extracellular space;
- uses second messenger systems (like IP3) activated by ligands binding to GPCR on the sarcolemma- epinephrine and ACh can activate GPCR linked to Gaq and activate PLC that leads to the production of IP3 and DAG.
fill in.
Innervation of smooth muscle varies widely by _________
location
describe single unit smooth muscle
- includes: GI tract, bladder, uterus, ureter
- these smooth muscle cells are linked by gap junctions
- characterized by spontaneous pacemaker activity also called slow waves
- the frequency of the slow waves sets up a pattern of action potentials that determine the frequency of action potentials
describe multiunit smooth muscle
- iris, ciliary muscle of the lens
- each muscle fiber acts as a separate motor unit. they are not coupled together by gap junctions
- these cells are innervated by the sympathetic and parasympathetic division of ANS
