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.