Control of Intacellular Calcium Flashcards

1
Q

Give 8 examples of cellular processes that are calcium sensitive

A

Fertilisation, Secretion, Neurotransmission, Metabolism, Contraction, Learning and memory, Apoptosis, Necrosis

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2
Q

How can Ca be metabolised?

A

It can’t

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3
Q

How does the cell regulate intracellular Ca concentration?

A

Based largely on moving Ca into and out of the cytoplasm

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4
Q

What is the extracellular concentration of Ca at rest

A

1-2mM

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5
Q

What is the intracellular concentration of Ca at rest?

A

100nM

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6
Q

What is the problem with the tight regulation of Ca levels?

A

The large gradient is energy expensive

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7
Q

What are the advantages of the large Ca gradient?

A

Changes in intracellular Ca occur rapidly and with little movement

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8
Q

What are the disadvantages of the large Ca gradient?

A

Ca overload leads to loss of regulation and cell death

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9
Q

What does the Ca gradient rely on?

A

The relative impermeability of the plasma membrane
The ability to expel Ca across the plasma membrane
Ca buffers
Intracellular Ca stores

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10
Q

What gives the ability to expel Ca across the plasma membrane?

A

Ca ATPase

Na-Ca Exchanger

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11
Q

What are the types of intracellular Ca stores?

A

Rapidly releasable

Non-rapidly releasable

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12
Q

What is membrane permeability regulated by?

A

The open/closed state of ion channels

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13
Q

What is the affinity of Ca ATPase?

A

High

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14
Q

What is the capacity of Ca ATPase?

A

Low

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15
Q

How does Ca ATPase work?

A

Intracellular Ca increases
Ca binds to calmodulin- a binding trigger protein
Calmodulin-Ca binds to Ca ATPase
Ca is removed from cell

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16
Q

What is the affinity of the Na/Ca Exchanger?

A

Low

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17
Q

What is the capacity of the Na/Ca Exchanger?

A

High

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18
Q

What is required to drive the Na/Ca Exchanger?

A

The Na gradient produced by Na/K-ATPase

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19
Q

How many Na are transported for how many Ca in the Na/Ca Exchanger?

A

3 Na in for 1 Ca out

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20
Q

What does the Na/Ca Exchanger do for the charge of the membrane?

A

Nothing- the antiporter is electrogenic

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21
Q

When does the Na/Ca Exchanger work best?

A

At resting membrane potential

22
Q

What do Ca buffers do?

A

Limit diffusion

23
Q

How do Ca buffers limit diffusion?

A

Through ATP and Ca binding proteins

24
Q

Give 4 examples of Ca binding proteins

A

Parvalbumin
Calreticulin
Calbindin
Calsequestin

25
Q

What does diffusion of Ca depend on?

A

The concentration of binding molecules, and their level of saturation

26
Q

What happens when some other proteins bind Ca?

A

It alters their function

27
Q

Give an example of a protein that changes function on Ca binding

A

Calmodulin

28
Q

How high can Ca levels rise when it is being used to regulate cellular activity?

A

~1µm

29
Q

How is intracellular Ca concentration increased?

A

Ca influx across the plasma membrane due to altered permeability
Ca release from ‘rapidly releasable’ and ‘non-rapidly releasable’ stores

30
Q

How does the permeability of the membrane allowing Ca influx change?

A

Voltage gated Ca channels

Receptor operation ion channels (ionotropic receptors)

31
Q

What controls Ca release from rapidly releasable stores?

A

G-protein coupled receptors

Ca induced Ca release

32
Q

What are voltage-gated calcium channels?

A

Channels that open to allow the influx of calcium down its concentration gradient, triggered by membrane depolarisation

33
Q

How does a receptor operated Ca channel work?

A

A ligand/agonist binds to the channel, opening it and allowing Ca to enter down its concentration gradient

34
Q

Where are stores of Ca set up inside the cell?

A

In the sarco/endoplasmic reticulum

35
Q

How are Ca stores set up in the sarco/endoplasmic reticulum set up?

A

By the SERCA protein.

Ca moved in using energy from ATP hydrolysis

36
Q

What happens once Ca has been moved into the sarco/endoplasmic reticulum?

A

It binds to proteins such as calsequestrin

37
Q

How do G-protein coupled receptors alter intracellular Ca concentration?

A

A ligand binds to the GPCR on the cell membrane, activating its Gαq subunit. This subunit then binds to the membrane phospholipid PIP2, releasing IP3, which in turn binds to its receptor on the sarco/endoplasmic reticulum, triggering the release of Ca down its concentration gradient into the cell

38
Q

How does Ca induced Ca release (CICR) work?

A

Ca binds to the Ryanodine receptor on the side of the sarco/endoplasmic reticulum, triggering the release of calcium down its concentration into the cell

39
Q

Give an example of an important physiological role for CICR?

A

In the cardiac myocyte

40
Q

Why is CICR important in the cardiac myocyte?

A

Ca entry through VOCCs following depolarisation of the membrane binds to the ryanodine receptors, causing an explosive release of large amounts of Ca from intracellular stores

41
Q

What are mitochondria important, regarding calcium?

A

They take up Ca when intracellular concentrations are high as a protective mechanism
Participate in normal Ca signalling

42
Q

Why can mitochondria take place in normal Ca signalling?

A

Due to microdomains

43
Q

What are microdomains?

A

Areas of cytoplasm with higher concentration of Ca due to their proximity to a channel

44
Q

What is the purpose of mitochondria taking up Ca?

A

Aids in buffering, regulating, signalling, and stimulation of ATP production

45
Q

How do mitochondria take up Ca?

A

Via a Ca uniporter

46
Q

What drives the Ca uniporter in mitochondria?

A

Respiration

47
Q

What does repetitive signalling require?

A

A return to the basal state

48
Q

What happens if there is too much Ca for too long?

A

It’s toxic to cell

49
Q

What does a return to basal Ca require?

A

Termination of signal
Ca removal
Ca store refilling

50
Q

How are Ca stores refilled?

A

By recycling of cytosolic Ca

Using Ca stored in mitochondria to replenish SR stores

51
Q

How does the Ca stored in mitochondria replenish the SR stores?

A

Via the store-operated Ca channel (SOC)