EC coupling and skeletal muscle contraction

Question 1

what triggers contraction in all types of muscle

Answer 1

increase of intracellular Ca2+

Question 2

what type of receptors are present at NMJs

Answer 2

ACh receptors

Question 3

what are the levels of organization in skeletal muscle

Answer 3

whole muscle -> muscle fiber (single cell) -> myofibril -> thick and thin filaments -> myosin and actin (protein molecules)

Question 4

what is the main component of thin filaments in skeletal muscle ?

Answer 4

actin

Question 5

what is the main component of thick filaments in skeletal muscle ?

Answer 5

myosin-II molecules

Question 6

what are the main features of a skeletal muscle cell ?

Answer 6

-elongated and cylindrical
- 10-100um in diameter and up to 75 cm in length
- multiple nuclei
abundance of mitochondria

Question 7

what is a myofibril

Answer 7

specialized contractile elements that extend the entire length of the muscle fiber

Question 8

how many myofibrils does a single muscle fiber contain

Answer 8

100-1000

Question 9

sarcomere

Answer 9

smallest functional unit in the muscle

Question 10

H - zone

Answer 10

portion of A band in which the is no over lap of thick and thin filaments

Question 11

M- line

Answer 11

center of the sarcomere, holds thick filaments in place

Question 12

A band

Answer 12

considered to be the dark band of the sarcomere

Question 13

I band

Answer 13

light band of sarcomere, located between two myosin and contains only the actin filaments of the neighboring sarcomeres

Question 14

Z-line

Answer 14

flat cytoskeletal disc which marks the boundary of a sarcomere

Question 15

what are the main features of thin filaments

Answer 15

• mainly actin
• also made up of troponin and tropomyosin
• double stranded a helices
• actin molecules have binding sites for myosin

Question 16

tropomyosin

Answer 16

prevents myosin cross bridges from attaching to thin filaments

Question 17

what are the three subunits of troponin ?

Answer 17

-Troponin T : binds to single molecule of tropomyosin
- Troponin C : binds to Ca2+
- troponin I : binds to actin and inhibits contraction

Question 18

what are the functions of troponin

Answer 18

stabilizes tropomyosin when Ca2+ levels are low and inhibits contraction

Question 19

how many actin monomers does a single tropomyosin molecule interact with

Answer 19

7

Question 20

how many tropomyosin molecules does each heterotrimer of troponin interact with

Answer 20

1

Question 21

where is tropomyosin located in the muscle fiber?

Answer 21

the thread like structures sit within the grove formed by the alpha helix of the thin filament and covers myosin binding sites

Question 22

what is each myosin-II molecule composed of ?

Answer 22

each molecule is a double trimer with : 2 intertwined heavy chains, 2 regulatory light chains and 2 alkali (essential) light chains.

Question 23

what are the three regions of the myosin heavy chains

Answer 23

tail, hinge and head

Question 24

what is the structure of the tail portion of the myosin molecules

Answer 24

a-helices that are intertwined

Question 25

the hinge region of the myosin molecule...

Answer 25

opens to form two globular heads

Question 26

what do the head regions of the myosin molecules give rise to ?

Answer 26

cross-bridges between thick and thin filaments of the sarcomere

Question 27

what are the two binding sites on the myosin heads ?

Answer 27

1) actin binding site 2) site for binding and hydrolyzing ATP

Question 28

what is the function of the alkali light chain ?

Answer 28

stabilizes the myosin head region

Question 29

what is the function of the regulatory light chain ?

Answer 29

regulates ATPase activity of myosin

Question 30

what regulates the activity of the regulatory light chains ?

Answer 30

they are regulated through phosphorylation by kinases

Question 31

why does an increase of intracellular Ca2+ trigger muscle contraction ?

Answer 31

removes the inhibition of crossbridge cycling

Question 32

what is the normal resting levels of intracellular Ca2+ ?

Answer 32

10^-7 M

Question 33

To what levels does intracellular Ca2+ levels rise to upon stimulation ?

Answer 33

greater than 10^-5M

Question 34

what does Ca2+ bind to in muscle fibers

Answer 34

Troponin C

Question 35

how many calcium binding sites does Troponin C have ?

Answer 35

2x high affinity and 2x low affinity

Question 36

high affinity Ca2+ binding sites participate in ...

Answer 36

binding troponin C to the thin filaments but Ca2+ binding to these sites does not change during muscle activation

Question 37

what does the binding of Ca2+ to the low affinity binding sites on troponin C induce ?

Answer 37

conformational change in the troponin complex

Question 38

Describe the conformational change that happens to the troponin complex

Answer 38

-Troponin I shifts allowing tropomyosin to move - Via Troponin T, tropomyosin is moved away from the myosin-binding site on actin and into the actin grove - this means that the myosin head can now interact with actin and engage with Cross bridge cycling

Question 39

what are the 5 steps of cross bridge cycling ?

Answer 39

1)ATP binding 2) ATP hydrolysis 3) cross bridge formation 4) release of Pi from myosin 5) ADP release

Question 40

what does ATP binding to the myosin head cause ?

Answer 40

dissociation of the actin- myosin complex ( released state)

Question 41

what does ATP hydrolysis cause in then cross-bridge cycle ?

Answer 41

myosin heads to return to their resting conformation

Question 42

what triggers the power stroke state in the cross-bridge cycle ?

Answer 42

The release of Pi

Question 43

describe the sliding filament mechanism

Answer 43

-thin filaments on each side of a sarcomere slide inwards over stationary thick filaments. -As they slide inwards the thin filaments pull the Z lines closer together so the sarcomere shortens. -All sarcomeres throughout the muscle fiber shorten simultaneously, the entire fiber shortens

Question 44

what happens to the A band during contraction?

Answer 44

determined by thick filaments so stays the same width

Question 45

what happens to the I band during contraction ?

Answer 45

thin filaments not overlapping thick so band width decreases

Question 46

what happens to the H zone during contraction

Answer 46

width decreases

Question 47

what happens to the distance between Z lines during contraction ?

Answer 47

decreases

Question 48

do the length of the thin and thick filaments shorten during contraction

Answer 48

No

Question 49

how long after death does rigor mortis begin

Answer 49

3-4 hours

Question 50

how long after death is rigor mortis complete

Answer 50

12 hours

Question 51

describe the process of rigor mortis

Answer 51

- intracellular Ca2+ begins to rise - Ca2+ lets regulatory proteins move aside allowing cross bridges to form, that were already charged with ATP prior to death - dead cells cannot produce ATP so actin and and myosin remain attached - rigor mortis subsides over the next several days when the protein involved start to degrade

Question 52

what is the process by which excitation triggers the increase of intracellular Ca2+ known as ?

Answer 52

excitation-contraction coupling (E-C) coupling

Question 53

how are Action potentials spread to the interior of skeletal muscles ?

Answer 53

traverse tubules (t-tubules)

Question 54

where are t-tubules located on the muscle ?

Answer 54

at the junctions between A and I bands between two sarcoplasmic reticulum

Question 55

what is the intracellular store for calcium

Answer 55

sarcoplasmic reticulum

Question 56

what is the "triad"

Answer 56

T-tubule between two sarcoplasmic reticulum

Question 57

what part of the SR is adjacent to the t-tubules ?

Answer 57

terminal cisternae

Question 58

what triggers a release of Ca2+ from the SR into the cytosol ?

Answer 58

spread of an action potential down a T-tubule

Question 59

what are the membrane proteins on the t- tubules known as and what do they do ?

Answer 59

dihydropyridine receptors (DHP) and they serve as voltage sensors

Question 60

what does the depolarization of t-tubules trigger ?

Answer 60

it activates the DHP receptors which in turn trigger the opening of Ca2+ release channels (ryanodine receptors) in the adjacent terminal cisternae, releasing Ca2+ into the the cytosol

Question 61

why are Ca2+ release channels also known as ryanodine receptors ?

Answer 61

they are locked in the open position by the plant protein ryanodine

Question 62

what spans the gap between the SR and t-tubule

Answer 62

foot-proteins that serve as Ca2+ release channels

Question 63

What is CICR and what does it play a critical role in ?

Answer 63

Ca2+ induced Ca2+ release, it is not necessary for contraction in skeletal muscle but plays a critical role in E-C coupling in cardiac muscle

Question 64

what removes Ca2+ from the cell ?

Answer 64

Na-Ca exchanger and Ca2+ pump (Ca2+ is dependent on hydrolysis of ATP)

Question 65

what concentrates Ca2+ within the Sarcoplasmic reticulum

Answer 65

Calreticulin and Calsequesterin

Question 66

how does Ca2+ enter the Sarcoplasmic reticulum ?

Answer 66

Ca2+ pumps

Question 67

what is the total duration of a Ca2+ pulse in a skeletal muscle fiber ?

Answer 67

1/20 of a second

Question 68

if prolonged contraction of a muscle is required what must occur

Answer 68

a series of calcium pulses must be initiated by a continuous series of repetitive action potentials

Question 69

By what factor does intracellular Ca2+ increase by when there is full excitation of the T-tubule/SR system

Answer 69

500-fold increase

Question 70

how is the contractile process turned off ?

Answer 70

Ca2+ is returned to the SR when electrical activity stops via Ca2+-ATPase pumps and thin filaments return to their resting position