M&R - Calcium Flashcards

1
Q

How is the internal concentration of Ca2+ significantly raised?

A

Ca2+ influx through Ca2+ channels

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2
Q

How is the structure of the alpha subunit of voltage gated Ca2+ channels similar to the voltage gated Na+ channels?

How do they differ?

A

Similar - split into repeats, voltage sensor, cause conformational change. Pore region which dictates permeability

Differs - slightly different as otherwise Na+ would flow through

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3
Q

What is an important type of alpha subunit of voltage gated Ca2+ channels?

How are they blocked?

A

L type

Blocked by DHP

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4
Q

What is necessary for a functional channel?

What is the role of associated subunits?

A

Pore forming subunit

Fine tune the properties and enable correct regulation of channel activity

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5
Q

What is the name of the synapse between a nerve and skeletal muscle fibre?

A

Neuromuscular junction

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6
Q

How is a signal passed from nerve to muscle?

A

Axon hillock has been raised to threshold

AP travels along axon

Gets to nerve terminal and release of transmitter causes contraction of skeletal muscle

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7
Q

What enzyme breaks down ACh?

A

Acetylcholine esterase

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8
Q

What is the importance of mitochondria in nerve terminals?

A

Reduce Ca2+ concentration for AP

Once AP has arrived, AP needs to decrease again for next AP. Ca2+ needs to be taken out of cytoplasm into store.

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9
Q

How is the transmitter released?

A
Ca2+ entry through Ca2+ channels
Ca2+ binds to snaptotgamin
Vesicle brought close to membrane
Snare complex make a fusion pore
Transmitter released through this pore
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10
Q

How many binding sites does a nicotinic receptor have?

When does it open?

What type of channel is it?
What molecules does it allow through?

A

Two.

Once two molecules of ACh are bound –> channel opens

Action channel - allows Na+ and K+ through in equal measures

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11
Q

Why does Na+ influx rather than K+ at the nicotinic receptor?

A

Channel opens

As the membrane potential is close to Ek, Na+ will influx and predominate to depolarise the cell causing an action potential

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12
Q

Where on the nicotinic receptor does ACh bind? How many alpha subunits are in the receptor?

What does the binding cause?

A

To each alpha subunit. 5 alpha subunit

Conformational change in the receptor causing the pore to open

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13
Q

What is transmitter release dependent on?

What happens to the end plate potentials in amplitude as external Ca2+ is lowered

A

Ca2+ entry

End plate potentials decrease in amplitude

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14
Q

What does curare cause?

And how?

A

Paralysis - by blocking the transmission between nerve and muscle

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15
Q

What are the two types of blockers of nicotinic receptors?

A

Competitive blockers

Depolarising blockers

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16
Q

How does a competitive blocker work?

Give an example

A

Binds at the nicotinic recognition site for ACh and closes channel

Tubocurarine

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17
Q

How does a depolarising blocker work?

Give an example.

A

Binds with nicotinic receptor and causes them to activate –> maintained depolarisation.

Area of membrane adjacent to NMJ are in Accomodation (Na+ channels inactivated. Small depolarisation has caused accumulation of inactivated NA+ channels

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18
Q

What are miniature end plate potentials?

A

Very small end plate potentials can still be recorded in response to single vesicle releasing its ACh.

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19
Q

How is an action potential generated in a muscle fibre?

A

ACh binding to nicotinic ACh receptors on muscle end plate, causing them to open and flow of cations causes depolarisation (end plate potential)

End plate potential depolarises the adjacent muscle membrane and activates voltage gated Na+ channels

AP travels along post synaptic nerve fibre and initiating an AP in the muscle

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20
Q

What type of disease is myasthenia gravis?

What are the symptoms?

How is it treated? And why?

A

Autoimmune disease targeting ACh receptors.

Drooping eyelids, profound weakened which increases with exercise.

ACh-esterase inhibitors - increase the amount of time ACh is in the synaptic cleft

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21
Q

How do nicotinic and muscarinic ACh receptors operate differently?

A

Nicotinic - produces a fast depolarisation because it is ligand gated ion channel

Muscarinic - does not have an ion channel. Produces a slower response because they are coupled to G proteins which trigger a cascade of events

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22
Q

How do action potentials cause Ca2+ channels to open in cell membranes?

A

AP arrives at the presynaptic membrane. The depolarisation causes voltage gated Ca2+ channels to open and the subsequent influx of Ca2+ down their concentration gradient

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23
Q

Why is calcium regulated by moving Ca2+ into and out of cytoplasm?

A

As it cannot be metabolised, that’s the way to cell regulates it

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24
Q

What are the advantages of a large inward gradient?

A

Changes in Ca2+ occur rapidly with movement of little Ca2+

Little has to be removed to re-establish resting conditions

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25
Q

What are the disadvantages of a large inward Ca2+ gradient?

A

Energy expensive

Inability to deal with Ca2+ easily leads to Ca2+ overload, loss of regulation and cell death.

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26
Q

What does the Ca2+ gradient rely on?

A

Relative impermeability of plasma membrane

The ability to expel Ca2+ across plasma membrane using Ca2+ATPase and Na+/Ca2+ exchanger

Ca2+ buffers

Intracellular Ca2+ stores - rapidly releasable and non rapidly releasable

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27
Q

What is the membrane permeability regulated by?

A

Open/close state of ion channels

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28
Q

How is Ca2+ expelled across the plasma membrane?

Describe what happens

A

Ca2+ATPase - as intracellular Ca2+ increases,
Ca2+ binds to calmodulin which binds to Ca2+ATPase and Ca2+ is removed from the cell
High affinity, low capacity

Na+/Ca2+ exchanger
Na+ gradient used as a driving force.. Transports 3Na+ into the cell and one Ca2+ out. Antiporter is Electrogenic = works best at resting membrane potential
Low affinity, high capacity

29
Q

How do Ca2+ buffers work?

What is diffusion dependent upon?

A

Ca2+ diffuses more slowly than predicted from ionic or hydrated radius
Ca2+ buffers limit diffusion through ATP and Ca2+ binding proteins
Diffusion dependent on concentration of binding molecules and level of saturation

30
Q

What are the two types of intracellular Ca2+ stores?

A

Rapidly releasable

Non-rapidly releasable

31
Q

What are trigger proteins?

A

Proteins that bind to Ca2+ not to buffer changes but to regulate activity

32
Q

How is Ca2+ elevated and returned to basal levels in cells?

A

Ca2+ influx across plasma membrane - voltage gated Ca2+ channels or receptor gated ion channels

Ca2+ release from rapidly releasable stores - GPCR, Ca2+ induced Ca2+ release.

Non rapidly releasable stores = mitochondria

33
Q

How can Ca2+ influx across a membrane?

A

Voltage gated Ca2+ channels

Receptor-operated ion channels

34
Q

What two ways can Ca2+ be rapidly released from stores?

A

G protein coupled receptors

Ca2+ induced Ca2+ release

35
Q

Why does Ca2+ store require ATP?

A

Ca2+ store is greater than the cytoplasm so a SERCA pump is needed.

36
Q

What regulates release from Ca2+ stores?

A

Ion channel - as there will be a large outward driving force when the store is full

37
Q

What are the two types of release channels that are activated to release Ca2+?

A

IP3 receptors or ryanodine receptors

38
Q

How does a GPCR release Ca2+?

A

A ligand binds to the GPCR on the cell membrane, activating Gq subunit. The subunit binds to phospholipid PIP2 releasing IP3 which in turn binds to its receptor on the Sarcoplasmic reticulum, triggering the release of calcium down its concentration gradient into the cell

39
Q

How does Ca2+ induced Ca2+ release Ca2+?

Where does the initial Ca2+ come from?

A

Ca2+ binds to the ryanodine receptor on the side of the sarcoplasmic recticulum, triggering the release of Ca2+ down its concentration gradient

Voltage gated Ca2+ channels, ionotropic receptors, intracellular stores

40
Q

What happens to Ca2+ at the very early part of the action potential?

A

Conditions will favour the reversal of Na+/Ca2+ exchanger (NCX) which will result in a small amount of Ca2+ entry.

As Ca2+ increases and membrane repolarisation starts, NCX will revert to Ca2+ extrusion and lower Ca2+.

Ca2+ will be pumped back into SR by SERCA in preparation for another AP

41
Q

What is the similarity Ca2+ channels have to Na+ channels in terms of activation and inactivation?

What allows prolongation of the depolarisation in cardiac cells?

A

Activation and inactivation occur but much slower

The above along with low K+ conductance at depolarised potentials

42
Q

What is the functional role of Ca2+ in muscle contraction?

A

Increase in cytoplasmic Ca2+ results in contraction

Ca2+ binds to troponin which undergoes conformational change, causing tropomyosin to move and reveal binding sites on actin for myosin head groups.

In the presence of ATP, myosin undergoes cycles of attachment and detachment, that, coupled with the movement of the head group results in sliding of the actin along myosin bundles and a shortening (contraction) of the myoctyes

43
Q

What is the role of the. Mitochondrial Ca2+ uptake?

A

Ca2+ buffering - regulate pattern and extent of Ca2+ signalling

Stimulation of mitochondria metabolism - match energy demand and supply

Role in cell death - apoptosis

44
Q

What within mitochondria do ca2+ use to signal?

A

Microdomains - areas of cytoplasm with a higher concentration of Ca2+ due to their proximity to a channel

45
Q

How does the cell return to basal Ca2+ levels?

A

Termination of signal

Ca2+ removal

Ca2+ store refilling

46
Q

Why is calcium regulated by moving Ca2+ into and out of cytoplasm?

A

As it cannot be metabolised, that’s the way to cell regulates it

47
Q

What are the advantages of a large inward gradient?

A

Changes in Ca2+ occur rapidly with movement of little Ca2+

Little has to be removed to re-establish resting conditions

48
Q

What are the disadvantages of a large inward Ca2+ gradient?

A

Energy expensive

Inability to deal with Ca2+ easily leads to Ca2+ overload, loss of regulation and cell death.

49
Q

What does the Ca2+ gradient rely on?

A

Relative impermeability of plasma membrane

The ability to expel Ca2+ across plasma membrane using Ca2+ATPase and Na+/Ca2+ exchanger

Ca2+ buffers

Intracellular Ca2+ stores - rapidly releasable and non rapidly releasable

50
Q

What is the membrane permeability regulated by?

A

Open/close state of ion channels

51
Q

How is Ca2+ expelled across the plasma membrane?

Describe what happens

A

Ca2+ATPase - as intracellular Ca2+ increases,
Ca2+ binds to calmodulin which binds to Ca2+ATPase and Ca2+ is removed from the cell
High affinity, low capacity

Na+/Ca2+ exchanger
Na+ gradient used as a driving force.. Transports 3Na+ into the cell and one Ca2+ out. Antiporter is Electrogenic = works best at resting membrane potential
Low affinity, high capacity

52
Q

How do Ca2+ buffers work?

What is diffusion dependent upon?

A

Ca2+ diffuses more slowly than predicted from ionic or hydrated radius
Ca2+ buffers limit diffusion through ATP and Ca2+ binding proteins
Diffusion dependent on concentration of binding molecules and level of saturation

53
Q

What are the two types of intracellular Ca2+ stores?

A

Rapidly releasable

Non-rapidly releasable

54
Q

What are trigger proteins?

A

Proteins that bind to Ca2+ not to buffer changes but to regulate activity

55
Q

How is Ca2+ elevated and returned to basal levels in cells?

A

Ca2+ influx across plasma membrane - voltage gated Ca2+ channels or receptor gated ion channels

Ca2+ release from rapidly releasable stores - GPCR, Ca2+ induced Ca2+ release.

Non rapidly releasable stores = mitochondria

56
Q

How can Ca2+ influx across a membrane?

A

Voltage gated Ca2+ channels

Receptor-operated ion channels

57
Q

What two ways can Ca2+ be rapidly released from stores?

A

G protein coupled receptors

Ca2+ induced Ca2+ release

58
Q

Why does Ca2+ store require ATP?

A

Ca2+ store is greater than the cytoplasm so a SERCA pump is needed.

59
Q

What regulates release from Ca2+ stores?

A

Ion channel - as there will be a large outward driving force when the store is full

60
Q

What are the two types of release channels that are activated to release Ca2+?

A

IP3 receptors or ryanodine receptors

61
Q

How does a GPCR release Ca2+?

A

A ligand binds to the GPCR on the cell membrane, activating Gq subunit. The subunit binds to phospholipid PIP2 releasing IP3 which in turn binds to its receptor on the Sarcoplasmic reticulum, triggering the release of calcium down its concentration gradient into the cell

62
Q

How does Ca2+ induced Ca2+ release Ca2+?

Where does the initial Ca2+ come from?

A

Ca2+ binds to the ryanodine receptor on the side of the sarcoplasmic recticulum, triggering the release of Ca2+ down its concentration gradient

Voltage gated Ca2+ channels, ionotropic receptors, intracellular stores

63
Q

What happens to Ca2+ at the very early part of the action potential?

A

Conditions will favour the reversal of Na+/Ca2+ exchanger (NCX) which will result in a small amount of Ca2+ entry.

As Ca2+ increases and membrane repolarisation starts, NCX will revert to Ca2+ extrusion and lower Ca2+.

Ca2+ will be pumped back into SR by SERCA in preparation for another AP

64
Q

What is the similarity Ca2+ channels have to Na+ channels in terms of activation and inactivation?

What allows prolongation of the depolarisation in cardiac cells?

A

Activation and inactivation occur but much slower

The above along with low K+ conductance at depolarised potentials

65
Q

What is the functional role of Ca2+ in muscle contraction?

A

Increase in cytoplasmic Ca2+ results in contraction

Ca2+ binds to troponin which undergoes conformational change, causing tropomyosin to move and reveal binding sites on actin for myosin head groups.

In the presence of ATP, myosin undergoes cycles of attachment and detachment, that, coupled with the movement of the head group results in sliding of the actin along myosin bundles and a shortening (contraction) of the myoctyes

66
Q

What is the role of the. Mitochondrial Ca2+ uptake?

A

Ca2+ buffering - regulate pattern and extent of Ca2+ signalling

Stimulation of mitochondria metabolism - match energy demand and supply

Role in cell death - apoptosis

67
Q

What within mitochondria do ca2+ use to signal?

A

Microdomains - areas of cytoplasm with a higher concentration of Ca2+ due to their proximity to a channel

68
Q

How does the cell return to basal Ca2+ levels?

A

Termination of signal

Ca2+ removal

Ca2+ store refilling