Control of Intacellular Calcium

Question 1

Give 8 examples of cellular processes that are calcium sensitive

Answer 1

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

Question 2

How can Ca be metabolised?

Answer 2

It can’t

Question 3

How does the cell regulate intracellular Ca concentration?

Answer 3

Based largely on moving Ca into and out of the cytoplasm

Question 4

What is the extracellular concentration of Ca at rest

Answer 4

1-2mM

Question 5

What is the intracellular concentration of Ca at rest?

Answer 5

100nM

Question 6

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

Answer 6

The large gradient is energy expensive

Question 7

What are the advantages of the large Ca gradient?

Answer 7

Changes in intracellular Ca occur rapidly and with little movement

Question 8

What are the disadvantages of the large Ca gradient?

Answer 8

Ca overload leads to loss of regulation and cell death

Question 9

What does the Ca gradient rely on?

Answer 9

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

Question 10

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

Answer 10

Ca ATPase

Na-Ca Exchanger

Question 11

What are the types of intracellular Ca stores?

Answer 11

Rapidly releasable

Non-rapidly releasable

Question 12

What is membrane permeability regulated by?

Answer 12

The open/closed state of ion channels

Question 13

What is the affinity of Ca ATPase?

Answer 13

High

Question 14

What is the capacity of Ca ATPase?

Answer 14

Low

Question 15

How does Ca ATPase work?

Answer 15

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

Question 16

What is the affinity of the Na/Ca Exchanger?

Answer 16

Low

Question 17

What is the capacity of the Na/Ca Exchanger?

Answer 17

High

Question 18

What is required to drive the Na/Ca Exchanger?

Answer 18

The Na gradient produced by Na/K-ATPase

Question 19

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

Answer 19

3 Na in for 1 Ca out

Question 20

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

Answer 20

Nothing- the antiporter is electrogenic

Question 21

When does the Na/Ca Exchanger work best?

Answer 21

At resting membrane potential

Question 22

What do Ca buffers do?

Answer 22

Limit diffusion

Question 23

How do Ca buffers limit diffusion?

Answer 23

Through ATP and Ca binding proteins

Question 24

Give 4 examples of Ca binding proteins

Answer 24

Parvalbumin
Calreticulin
Calbindin
Calsequestin

Question 25

What does diffusion of Ca depend on?

Answer 25

The concentration of binding molecules, and their level of saturation

Question 26

What happens when some other proteins bind Ca?

Answer 26

It alters their function

Question 27

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

Answer 27

Calmodulin

Question 28

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

Answer 28

~1µm

Question 29

How is intracellular Ca concentration increased?

Answer 29

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

Question 30

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

Answer 30

Voltage gated Ca channels | Receptor operation ion channels (ionotropic receptors)

Question 31

What controls Ca release from rapidly releasable stores?

Answer 31

G-protein coupled receptors | Ca induced Ca release

Question 32

What are voltage-gated calcium channels?

Answer 32

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

Question 33

How does a receptor operated Ca channel work?

Answer 33

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

Question 34

Where are stores of Ca set up inside the cell?

Answer 34

In the sarco/endoplasmic reticulum

Question 35

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

Answer 35

By the SERCA protein.  | Ca moved in using energy from ATP hydrolysis

Question 36

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

Answer 36

It binds to proteins such as calsequestrin

Question 37

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

Answer 37

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

Question 38

How does Ca induced Ca release (CICR) work?

Answer 38

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

Question 39

Give an example of an important physiological role for CICR?

Answer 39

In the cardiac myocyte

Question 40

Why is CICR important in the cardiac myocyte?

Answer 40

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

Question 41

What are mitochondria important, regarding calcium?

Answer 41

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

Question 42

Why can mitochondria take place in normal Ca signalling?

Answer 42

Due to microdomains

Question 43

What are microdomains?

Answer 43

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

Question 44

What is the purpose of mitochondria taking up Ca?

Answer 44

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

Question 45

How do mitochondria take up Ca?

Answer 45

Via a Ca uniporter

Question 46

What drives the Ca uniporter in mitochondria?

Answer 46

Respiration

Question 47

What does repetitive signalling require?

Answer 47

A return to the basal state

Question 48

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

Answer 48

It’s toxic to cell

Question 49

What does a return to basal Ca require?

Answer 49

Termination of signal  Ca removal  Ca store refilling

Question 50

How are Ca stores refilled?

Answer 50

By recycling of cytosolic Ca  | Using Ca stored in mitochondria to replenish SR stores

Question 51

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

Answer 51

Via the store-operated Ca channel (SOC)