Lecture 11: Excitation-Contraction Coupling and the Cross-Bridge Cycle

Question 1

What is the name of the connective tissue that surrounds muscle fibres?

Answer 1

endomysium

Question 2

What is the name of the connective tissue that surrounds that fasicle?

Answer 2

perimysium

Question 3

What is the name of the connective tissue that surrounds the muscle?

Answer 3

epimysium

Question 4

What is the purpose of the veins and capillaries surrounding the fasicles?

Answer 4

to supply the muscle fibres with O2 and nutrients

Question 5

What is the purpose of the nerves that surround the muscle fibres?

Answer 5

to travel from the spinal cord to the muscle cells to innervate them

Question 6

Where is Ca2+ stored in the muscle fibres?

Answer 6

in the sarcoplasmic reticulum

Question 7

What is the purpose of the T-tubule?

Answer 7

to conduct the depolarisation into the muscle cell

Question 8

What is the name of the skeletal muscle membrane?

Answer 8

sarcolemma

Question 9

Where does the sarcoplasmic reticulum sit?

Answer 9

right next to the T-tubule

Question 10

How does the AP that is conducted along the sarcolemma get inside the muscle cell?

Answer 10

via the T-tubule which propagates it inside the cell

Question 11

What is the purpose of the mitochondria in the muscle fibre?

Answer 11

to generate ATP to be used for muscle contraction via the cross-bridge cycle

Question 12

How does Ca2+ get into the SR?

Answer 12

it is actively pumped from the cytosol into the SR by a Ca2+ pump which requires ATP

Question 13

How does the action potential get propagated along the sarcolemma?

Answer 13

via the opening of voltage gated ion channels which brings it into the muscle

Question 14

What is the voltage sensor?

Answer 14

it is the dihydropyridine receptor which senses the action potential in the T-tubule and it relays it to the Ca2+ channel through physical coupling which opens the Ca2+ channel

Question 15

What causes the Ca2+ channel to open?

Answer 15

when the voltage sensor senses the action potential and relays it to the channel through physical coupling

Question 16

What is the name of the voltage sensor which opens the Ca2+ channel?

Answer 16

dyhydropyridine

Question 17

What is the name of the Ca2+ channel?

Answer 17

ryanodine receptor

Question 18

Which direction does Ca2+ flow when the ryanodine receptors open in the membrane of the SR?

Answer 18

out of the sarcoplasmic reticulum (into the cytosol)

Question 19

What is the name of the Ca2+ pump which pumps Ca2+ back into the SR?

Answer 19

SERCA

Question 20

What happens to the Ca2+ once it is in the cytosol?

Answer 20

it can interact with the actin

Question 21

What happens if the Ca2+ stay high in the cytosol for too long?

Answer 21

the muscle contract for too long and there is continued force development

Question 22

What is heat a biproduct of?

Answer 22

muscle activity (muscle contraction)

Question 23

Why is heat a necessary biproduct?

Answer 23

because it maintains our body temperature

Question 24

How is heat produced?

Answer 24

through processes which generate ATP and use ATP

Question 25

Give an example of where heat is generated during a muscle contraction

Answer 25

when Ca2+ is pumped back into the SR via SERCA, SERCA hydrolyses ATP to ADP and phosphate to pump Ca2+ back into the sarcoplasmic reticulum and this generates heat. The production of new ATP also produces heat

Question 26

What is is called when the body temperature increases above normal?

Answer 26

hyperthermia

Question 27

What is it called when the body temperature decreases below normal?

Answer 27

hypothermia

Question 28

What can hyperthermia cause? Why is this?

Answer 28

it can lead to nausea, vomiting, headaches, confusion and death because many processes stop working

Question 29

What causes malignant hyperthermia?

Answer 29

mutations in ryanodine receptor or the dihydropyridine receptor (DHPR)

Question 30

What is malignant hyperthermia?

Answer 30

an autosomal dominant, life-threatening disease

Question 31

What triggers malignant hyperthermia?

Answer 31

volatile anaesthetics (ones that you inhale)

Question 32

What happens during malignant hyperthermia?

Answer 32

The volatile anaesthetics interfere with the ryanodine receptor or the DHPR receptor with the mutations. These anaesthetics increase the function of these voltage sensors or Ca2+ channels causing a massive increase in the amount of Ca2+ released through the receptors. This excessive Ca2+ released from the SR store, there is muscle rigidity, spontaneous muscle contractions which leads to hyper-metabolic state because the Ca2+ has to be pumped back into the SR which uses ATP (which requires ATP production) which causes lots of heat

Question 33

In the autoimmune disease myasthenia gravis, a rapid and prolonged sequence of action potentials at the NMJ will initiate progressively weaker muscle contraction BECAUSE more ACh is released from the motor neuron during each successive action potential

Answer 33

the first statement is true and the second one is false

Question 34

Which is the thin filament, actin or myosin?

Answer 34

actin is the thin filament and myosin is the thick filament

Question 35

What does a single action potential tigger?

Answer 35

a twitch | a short period of force generation which lasts just a short period of time

Question 36

What two states can the myosin head be in?

Answer 36

flexed or energised (when it has ATP hydrolysed)

Question 37

What is Mg2+ important for?

Answer 37

ATP hydrolysis

Question 38

Describe the cross bridge cycling

Answer 38

the interaction between myosin and actin which generates force and allows these filaments to slide across each other

Question 39

What does the thin actin filament have?

Answer 39

tropomyosin and troponin associated with them

Question 40

What is tropomyosin?

Answer 40

This long thin beaded structure which runs across the entire length of actin which normally blocks the myosin binding sites

Question 41

Where are the myosin binding sites?

Answer 41

on the actin | these are normally hidden by tropomyosin

Question 42

What is troponin?

Answer 42

it is part of tropomyosin and it has a calcium binding site on it troponin is the calcium sensor which senses calcium and causes a conformational change in tropomyosin to expose these myosin binding sites

Question 43

Describe myosin

Answer 43

there are heavy chains and light chains and two heads

Question 44

What are the two heads of myosin for?

Answer 44

both heads have both actin binding sites on the end of the head and ATP binding sites

Question 45

Why can't myosin bind to actin under resting conditions? ie. low sarcoplasmic Ca2+ (Ca2+ inside the muscle cell not the sarcoplasmic reticulum)

Answer 45

because tropomyosin is blocking the myosin binding sites

Question 46

In order to get interaction between actin and myosin to generate skeletal muscle contraction, what needs to happen?

Answer 46

tropomyosin needs to be removed from the myosin binding sites

Question 47

When Ca2+ is released from the sarcoplasmic reticulum into the inside of the muscle cell, what happens?

Answer 47

Ca2+ binds to troponin which causes a conformational change which causes tropomyosin to move off the myosin binding sites which allows the myosin head to bind and engage with actin. This is cross bridge formation

Question 48

At the "end" of the cycle, where is ATP bound?

Answer 48

if ATP is available, it will bind the ATP binding sites on the myosin head

Question 49

When ATP binds to the ATP binding site on the myosin head, what happens (at the "end of the cycle)?

Answer 49

the myosin head can disengage/come off the actin

Question 50

What happens to the ATP when it is bound to the myosin head? What does this cause?

Answer 50

it is hydrolysed to ADP and phophate which energises the myosin head so it goes from a flexed position (relaxed) to an energised extended position

Question 51

Where so the ADP and Pi go when the myosin head is energised?

Answer 51

they stay on the myosin head

Question 52

If the myosin head is stimulated but there is no Ca2+ around, what happens?

Answer 52

the process stops here, there is no cross bridge formation because the myosin sites are blocked by tropomyosin

Question 53

When the myosin head binds to actin, in order to generate force, what has to happen?

Answer 53

the ADP and Pi are released which flexes the myosin head and force is generated

Question 54

To get repeating of the cycle after there has been force generated, what has to happen?

Answer 54

the myosin head needs to come off the actin so ATP binds

Question 55

The cross bridge cycle requires ATP. What happens when there is no ATP around?

Answer 55

the myosin head stays attached to the actin and so the muscle stays stiff (rigor mortis after death)