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Physiology and Pharmacology > E-C coupling > Flashcards

E-C coupling Flashcards

1
Q

State the primary function of muscle

A

Generate force or movement in response to a physiological stimulus

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2
Q

What do muscles do in order to generate a mechanical response?

A

Transduce a chemical or electrical signal

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3
Q

What is the trigger for contraction of all 3 types of muscle?

A

An increase in Ca2+

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4
Q

What causes skeletal muscle to contract?

A

Contracts in response to neuromuscular synaptic transmission

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5
Q

A skeletal muscle fibre has a single NMJ where Ach receptors are located. What happens when ACh is released from the pre-synaptic nerve terminal?

A

It binds to nicotinic ACh receptors at the NMJ

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6
Q

Are nicotinic ACh receptors selective or non-selective?

What happens when ACh binds to them?

A

Non-selective cation channels

Open in response to ACh binding, resulting in depolarisation of Em known as end plate potential (epp)

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7
Q

What happens if the epp exceeds threshold for activating V-gated Na+ channels?

A

An action potential is generated

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8
Q

How is ACh rapidly inactivated?

A

Ach-esterase

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9
Q

How are skeletal muscles arranged?

A

Striated

Highly organised internal arrangement

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10
Q

What components make up a single skeletal muscle cell?

A
  • Multiple nuclei
  • Abundance of mitochondria
  • 10-100 um in diameter and up to ~75cm in length
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11
Q

Define myofibrils

A

Specialised contractile elements that extend the entire length of the muscle fibre

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12
Q

What does thick and thin myofibril mean?

A

Thick- special assemblies of the protein myosin

Thin- made up primarily of the protein actin

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13
Q

Describe what an A band is made up of

What is the H zone?

A

Stacked set of thick filaments along with the portions of the thin filaments that overlap on both ends of the thick filaments

H-zone: The lighter area within the middle of the A band, where the thin filaments do not reach

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14
Q

What is the M-line and where is it located?

A

A system of supporting proteins that hold the thick filaments together vertically within each stack

Extends vertically down the middle of the A bnad within the centre of the H zone

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15
Q

What does the I band consist of and what is it visible in the middle of each I band?

A

The remaining portions of the thin filaments that dont project into the A band

Dense verticle line called the Z line

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16
Q

What is the area between two Z-lines called and what is it?

A

Sarcomere

Functional unit of the skeletal muscle

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17
Q

What are the characterisitics of the Z-line?

A

Flat, cytoskeletal disc that connects the thin filaments of the two adjoining sarcomeres

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18
Q

What is the width of a sarcomere?

A

2.5 um

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19
Q

List the levels of organisation in a skeletal muscle?

A
  • Whole skeletal muscle (organ)
  • Muscle fibre (single cell)
  • Myofibril (specialised intracellular structure)
  • Thick and thin filaments (cytoskeletal elements)
  • Myosin and actin (protein molecules)
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20
Q

What do the thin filaments consist of?

A

Actin, tropomyosin and troponin

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21
Q

Explain the backbone of the thin filaments

A

A double stranded alpha helical polymer of filamentous-actin (F-actin molecules

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22
Q

What is F-actin associated with?

A

2 regulatory, actin proteins- tropomyosin and troponin

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23
Q

What does tropomyosin consist of?

A

2 identical a-helices that coil around eachother

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24
Q

head-to-tail contact between neighbouring tropomyosin molecules forms a ribbon that lies alongside the groove of the actin helix and physically covers the binding sites on actin molecules for attachment to what?

A

Myosin cross bridges

Prevents thin filaments attaching to cross bridges

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25
Q

Each heterotrimer of troponin interacts with a single molecule of tropomyosin, which inturn interacts directly with 7 actin monomers
What types of troponin are there?

A

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

26
Q

What are thich filaments composed of?

A

Multiple myosin-II molecules

27
Q

Each myosin-II molecule is a double trimer composed of what?

A
  • 2x intertwined heavy chains
  • 2x regulatory llight chains
  • 2x alkali (or essential) light chains
28
Q

What are the three regions of the 2 heavy chains?

A

A tail, hinge and a head region

29
Q

What is the tail, hinge and head portion of the thick filaments?

A

Tail- a-helices that intertwine

Hinge- the molecule opens to form 2 globular heads

Head- (S1 fragments) are the cross bridges between the thick and thin filaments of the sarcomere

30
Q

What do the heads of the heavy chains in thick filaments possess?

A

Binding site for actin and a site for binding and hydrolysing ATP

31
Q

What do the head portions of each myosin form?

What do these components do?

A

Forms a complex with 2 light chains, 1 alkali and 1 regulatory

Alkali- stabilises the myosin head region
Regulatory- regulates the ATPase activity of myosin. The activity of this chain is regulated via phosphorylation by kinases

32
Q

What happens to myosin-II heads in muscle contraction?

Where does the energy come from?

A

Bind to actin where the cross bridges become distorted and finally the myosin heads detach from actin

Hydrolysis of ATP

33
Q

How does Ca2+ cause contraction?

A

Removes the inhibition of crossbridge cycling

34
Q

Troponin contains troponin C that binds what?

A

Ca2+

35
Q

What are the 5 steps of the cross-bridge cycle?

A

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

36
Q

What is the sliding filament mechanism?

A

Cross-bridge interaction between actin and myosin bringing about muscle contraction

37
Q

What filaments on each side of the sarcomere slide inward over the stationary thick filaments?
What happens when they slide inwards?

A

Thin filaments

The thin filaments pull the Z-line (to which they are attached) closer together, so the sarcomeres shorten

38
Q

Do the length of the filaments shorten during contraction and why?

A

No

Due to interactions of the filaments sliding over one another

39
Q

What happens to the A, I band, H and Z zone during contraction?

A

A band- Determined by thick filaments so stays the same width

I band- Thin filaments not overlapping thick, so I band width decreases

H zone- Within A band, thick filaments not overlapping thin so width decreases

Z-line- Distance between decreases

40
Q

What is rigor mortis and when does it occur?

A

“Stiffness of death”

3-4 hours after death and completes in ~12 hours

41
Q

What happens during rigor mortis?

A
  • Ca2+ rises after death
  • The Ca2+ allows the regulatory proteins aside and lets actin bind the myosin cross bridges that are charged with ATP
  • Dead cells cant produce more ATP so actin and myosin cannot detach
42
Q

When does rigor mortis begin to reside?

A

The next several days after death as proteins involved start to degrade

43
Q

What does E-C coupling stand for?

A

Excitation-contraction

44
Q

What is the plasma membrane of a muscle cell also known as?

In skeletal muscle, what do they take the form of?

A

Sarcolemma

Transverse or T tubules

45
Q

Where to T tubules penetrate the muscle- two points?

A

Junctions of the A and I bands

46
Q

What is the muscle cell equivalant of the endoplasmic reticulum and what does it serve as storage for?

A

Sarcoplasmic reticulum

Ca2+

47
Q

What is the combination of the T tubule membrane and its two neighhbouring cisternae called? What is the structures role?

A

Triad

Coupling of excitation to contraction in skeletal (and cardiac) muscle

48
Q

What happens when the T tubule is depolarised?

A

Leads to Ca2+ release from the SR at the triad

49
Q

What do the V-gated channels known as tetrads do?

A

Function as the voltage sensor in E-C coupling

50
Q

Depolarisation evokes conformational changes in each of the four L-type Ca+ channels and has two effects. What are these effects?

A

Conformational changes allowing:

  • Ca2+ to enter through the four channel pores
  • Induce conformation change in each of the four subunits of Ca2+ channel located in the SR membrane
51
Q

Where do Ca2+ channekls cluster?

A

In the portion of the SR that face the T tubules

52
Q

What happens upon opening of the Ca2+ release channels in the SR?

A

Ca2+ stored in the SR enter the cytosol leading to a rapid increase in [Ca2+]i

53
Q

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

A

Local elevations in [Ca2+] can also activate the release channel in skeletal muscle

Plays a crucial role in E-C coupling in cardiac muscle

54
Q

What does terminating contraction in all 3 muscle types require?

A

re-uptake of Ca2+ into the SR

55
Q

What two ways can the cell extrude Ca2+?

A
  • An Na-Ca exchanger (NCX)

- A Ca2+ pump at the PM (PMCA)

56
Q

How is Ca2+ re-uptake mediated?

A

SERCA-type Ca2+ pump

57
Q

Where is Calreticulin found in high concentrations? and what is it?

A

Within the SR of smooth muscle

Principal Ca2+ binding protein

58
Q

What is the excitatory pulse used for?

A

If the contraction is to continue for longer periods, a series of calcium pulses must be initiated by a continous series of repetitve action potentials

59
Q

Contractile activity far outlasts the electrical activity that initiated. What is the time delay called?

A

Latent period

60
Q

When is the contraction process turned off?

A

When Ca2+ is returned to the SR when electrical activity stops
The thin filaments then return passively to their resting position

61
Q

What part of the sarcomere does not change in length?

A

A band - dark band

Overlap between thick and thin filaments

Physiology and Pharmacology (22 decks)

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