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MED221A/B Lectures > MSK 14 - Skeletal muscle 1 > Flashcards

MSK 14 - Skeletal muscle 1 Flashcards

1
Q

what are the 4 roles of skeletal muscle

A

produce force and movement necessary for life

provide support

produce heat

regulate glucose homeostasis

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2
Q

what is the morphological classification of muscles - based on structure

A

striated = skeletal and cardiac muscle

non striated = smooth muscle

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3
Q

is skeletal muscle voluntary or involuntary movements

A

voluntary

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4
Q

what happens at the neuromuscular junction in terms of AP and what does it cause

A

nerve action potential arrives via alpha motor neuron to the neuromuscular junction and AP spreads along fibres leading to excitation contraction coupling

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5
Q

what happens in excitation contraction coupling in terms of Ca2+

A

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

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6
Q

what are the 2 myofilament proteins found in a sarcomere

A

myosin and actin

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7
Q

what is a muscle cell called

A

myofibre

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8
Q

what is the smallest unit of a muscle

A

myofibres

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9
Q

what is wrapped around the myofibre

A

endomysium

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10
Q

what is beneath the endomysium

A

plasma membrane - sarcolemma

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11
Q

what is a bundle of myofibres called in a muscle

A

fascicles

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12
Q

what is wrapped around a fascicle

A

perimysium

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13
Q

what wraps around a bundle of fascicles

A

epimysium - outer connective tissue

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14
Q

what is the structure of skeletal muscle fibres in terms of innervation, branched/unbranched and shape

A

innervated via neural networks

unbranched long cylindrical (varying lengths)

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15
Q

how are skeletal muscle fibres arranged relative to one another and where are they connected to one another

A

stacked side by side but not connected to one another apart from at the ends of the muscles fibres to the tendon

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16
Q

why are skeletal muscles multinucleated

A

during formation of skeletal muscle cells precursor myoblasts that each have a nucleus and fuse together to form muscle fibre

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17
Q

do myofibres have connections to other myofibres

A

no

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18
Q

describe T tubules in terms of what they are, their orientation and what they do

A

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

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19
Q

what does the sarcoplasmic reticulum do

A

store calcium ions

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20
Q

what does calcium ions do

A

triggers cross bridge cycle

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21
Q

what is a myofibril a bundle of

A

a bundle of contractile proteins

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22
Q

what is the A band of the myofibril made up of and what is its appearance

is it isotropic/anisotropic

A

made up of myosin filaments (dark/thick)

anisotropic

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23
Q

what is the I band of the myofibril made up of and what is its appearance

is it isotropic/anisotropic

A

thin actin filaments

isotropic

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24
Q

what holds the I band in position on a myofibril

A

Z disc

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25
Q

what does the Z disc hold in position

A

the I band

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26
Q

where is the M line in a myofibril and what does it do

A

middle of the H zone

gives contractile proteins structure

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27
Q

what is a sarcomere where are its borders

A

one contractile unit of myofibiril

from z disc to z disc

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28
Q

what are the junctional areas of the sarcoplasmic reticulum near the T tubules called

A

terminal cisterna

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29
Q

what is the name of the structure of the 2 terminal cisternae and the T tubule

A

triad

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30
Q

where are T tubules located in relation to the myofibril zones

A

at the junction of overlap between the A and I bands

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31
Q

what is calsequestrin and what does it do

A

protein within the sarcoplasmic reticulum that binds the Ca2+ (can bind aorund 40 Ca2+ per protein)

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32
Q

what receptors does calsequestrin link to and what does this do

A

links to ryanodine receptors that are release channels from the SR

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33
Q

what does the triad allow

A

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

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34
Q

what are the 4 sarcomeric proteins that are associated with the thin actin filaments

A

titin

troponin

nebulin

tropomyosin

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35
Q

what does titin do

A

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

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36
Q

what structures does the titin protein connect

A

Z discs and thick/myosin filaments

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37
Q

thin actin filaments are held together where at each end of the sarcomere

A

at the Z disc

38
Q

what does the hinge region of the myosin filament allow

A

allows movement of the head by 45 degrees and causes Z discs to move closer together

39
Q

what do the myosin heads contain

A

contains ATPase and binding sites for actin/thin filaments

40
Q

how many heads are on each myosin filament

A

2

41
Q

what is the actin chain made up of

A

globular G-actin molecules

42
Q

what structures on actin contain the myosin binding sites

A

troponin

43
Q

what is troponin

A

troponin C is on the actin filaments and contains the myosin binding sites

44
Q

what holds the G-actin molecules together

A

nebulin

45
Q

what does nebulin do

A

holds the G-actin molecules together

46
Q

what does tropomyosin do

A

covers myosin binding sites on actin filaments

47
Q

what covers myosin binding sites on actin filaments

A

tropomyosin

48
Q

what happens to tropomyosin at rest

A

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

49
Q

what happens to troponin C when there is Ca2+ bound to it

A

there is movement of troponin I and troponin T which moves aside tropomyosin and exposes the myosin binding sites on actin

50
Q

what band does myosin form

A

A band

51
Q

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

A

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

52
Q

what is the actin filament composed of

A

composed of globular (G) actin molecules linked to two strands twisted into a helix to form filamentous (F) actin

53
Q

is actin held at fixed lengths

A

yes by proteins

54
Q

what band does actin filaments make up

A

I bands

55
Q

how are tropomyosin orientated relative to the F actin

A

rod shaped Tm lies along each F actin in a groove

56
Q

what other proteins is tropomyosin associated with and what do they comprise

A

3 proteins

TnT, TnC, TnI

comprises the troponin complex

57
Q

of TnT, TnC, TnI where does Ca2+ bind

A

on TnC

58
Q

what does nebulin do to help the F actin filaments

A

aligns twisted F actin filaments

59
Q

in the troponin complex what does TnT do

A

Troponin tropomyosin

positions the complex on the tropomyosin molecule and holds tropomyosin in place

60
Q

in the troponin complex what does TnC do

A

troponin calcium

contains the Ca2+ binding sites

61
Q

how many Ca2+ binding sites are there on TnC and what is the affinity strength

A

up to 4 Ca2+ binding sites for each TnC - some are high affinity some are low affinity

62
Q

in the troponin complex what does TnI do

A

troponin inhibitor

binds actin and inhibits the myosin head from binding to the actin binding site when cytosolic Ca2+ is low

63
Q

what two components make up the Ca2+ sensitive switch

A

Tn complex (TnC, TnT, TnI) and Tropomyosin

64
Q

what does the Tn complex and Tm create

A

the Ca2+ sensitive switch

65
Q

what happens when Ca2+ is high and bound to TnC binding site

what needs to be present for binding to continue

A

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

66
Q

the ability of a muscle fibre to develop force depends on what

A

the interaction of contractile proteins actin and myosin

67
Q

myosin has a high affinity for actin binding site when what is bound

A

when ADP.P is bound

68
Q

when myosin is bound with ADP.P what effect does this have on the affinity for actin binding site

A

increases affinity

69
Q

in the relaxed state what orientation are the myosin heads in and what is the binding site like

A

myosin heads at 90 degrees

tropomyosin blocks the binding site from myosin head

70
Q

describe the sequence of events of how a muscle shortens due to actin and myosin in the cross bridge cycle

A

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

71
Q

describe the release of myosin from the myosin actin binding site and how this happens - 5 steps

A

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

72
Q

what happens if there is no ATP and the end of the cross bridge cycle

what is this state called

A

myosin head remains tightly bound to actin - rigor state

73
Q

what are the 2 roles of ATP in the cross bridge cycle

A

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

74
Q

when does relaxation come about for a muscle

A

when Ca2+ concentration in cytosol decreases

75
Q

how is Ca2+ taken back up and where does it go

A

taken back up into longitudinal sarcoplasmic reticulum membrane by ATPase (calcium pump)

once back in SR, Ca2+ binds to calsequestrin

76
Q

when at rest and cytosolic Ca2+ levels are low, what inhibits cross bridge cycle

A

thin filament proteins troponin (TnC, TnI, TnT) and tropomyosin

77
Q

cross bridge cycling occurs and generates force as long as what two conditions are met

A

as long as Ca2+ remains high and ATP is present

78
Q

what structure hangs in the space between the T tubule and the junctional SR at the triad

A

the extracellular portion of the ryanodine receptor (electron dense feet region of ryanodine receptor)

79
Q

what do the ryanodine receptors do

A

link proteins in T tubule membrane dihydropyridine receptor (DHPR)

80
Q

how does the DHPR and ryanodine receptors interact

A

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

80
Q

what type of receptor is the DHPR

A

voltage gated Ca2+ channels in sarcolemma

81
Q

are DHPRs functional Ca2+ channels in skeletal muscle why

A

no

because there is no effective transfer of Ca2+ across the T tubule membrane

82
Q

what are ryanodine receptors (RyR)

A

Ca2+ release channels of SR

83
Q

what does it mean when we say that troponin C binds up to 4 Ca2+ cooperatively

A

when one or 2 sites bind Ca2+, the other sites bind Ca2+ more easily

84
Q

how many high affinity and low affinity binding sites are there on troponin C

A

2 high affinity

2 low affinity

85
Q

what type of RyR is in skeletal muscle

A

RyR1

86
Q

where do the RyRs exist

A

at the terminal cisternae of junctional SR

87
Q

what inhibits skeletal RyR activation

A

cytosolic Mg2+

88
Q

how does voltage sensor DHPR activation overcomes Mg2+ inhibition

A

sense depolarisation of membrane around DHPR and causes them to interact with RyR and opens them

89
Q

what overcomes the Mg2+ inhibition of RyR

A

DHPR activation

90
Q

what are the benefits of voltage dependent excitation contraction coupling - 4 reasons

A

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+

MED221A/B Lectures (23 decks)

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