Cytosolic Control of Calcium

Question 1

Give approximate values for calcium concentration inside and outside a cell.

Answer 1

1-2mM outer

100nM inner

Question 2

What is an advantage of having such a large concentration difference of calcium?

Answer 2

Change in calcium concentration inside the cell will occur rapidly with little movement of calcium.

Question 3

Describe the function of PMCA

Answer 3

Expels calcium from the cell.
Calcium inside the cell increases and binds to calmodulin (a trigger protein). Ca-calmodulin binds to PMCA which removes calcium.
High affinity and low capacity

Question 4

Describe the function of NCX

Answer 4

Secondary antiport active transporter.
Electrogenic so works best at a resting membrane potential.
Low affinity and high capacity, can be reversed.

Question 5

Describe the function of calcium buffers

Answer 5

Limit diffusion - calcium can only travel around 0.1-0.5 micrometers before encountering a binding molecules.
Depends on the concentration of binding molecules and level of saturation

Question 6

Give an example of a protein which calcium binds to alter it’s function.

Answer 6

Synaptotagmin
Calmodulin
Troponin

Question 7

Describe the function of VOCC

Answer 7

Voltage operated calcium channel. Allows the influx of calcium into a cell.

Question 8

Give an example of a ligand-gated calcium channel which is a glutamate receptor.

Answer 8

NMDA

AMPA

Question 9

Describe conformation coupling and give an example of a protein which utilises it.

Answer 9

When the conformational change of a protein in the membrane allows it to interact with another.
CICR with VOCC

Question 10

What is the function of the Gαs subunit in a GPCR?

Answer 10

Stimulates adenylate cyclase which increases production of cAMP so it can modify PKA.

Question 11

What is the function of the Gαi subunit in a GPCR?

Answer 11

Inhibits adenylate cyclase so production of cAMP is reduced, decreasing PKA activity.

Question 12

What is the function of the Gαq subunit in GPCR?

Answer 12

Stimulates phospholipase C which causes increased production of IP3 and DAG.

Question 13

What is the function of the βγ subunit in GPCR?

Answer 13

Regulates opening and closing of channels.

Question 14

Describe how depolarisation of the membrane allows calcium influx.

Answer 14

VOCC is opened, allowing calcium influx. This activates RyR to increase calcium release from the ER, allowing fast and explosive release of calcium.
NCX reverses after depolarisation, contributing slightly to calcium entry.

Question 15

What is the major route to refill the ER?

Answer 15

SERCA

Question 16

Which organelle has non rapidly releasable intracellular calcium intake?

Answer 16

Mitochondria

Question 17

Describe calcium uptake into the mitochondria.

Answer 17

A uniporter allows calcium uptake and utilises the driving force from respiratory chain protein production. Low affinity and high capacity.

Question 18

What is the role of calcium uptake into the mitochondria.

Answer 18

Calcium buffering - regulates pattern and extent of calcium signalling.

Stimulates mitochondrial metabolism - matches energy demand and supply.

Role in cell death - apoptosis/altered redox potential.

Question 19

How are calcium stores refilled?

Answer 19

Recycling cytosolic calcium (e.g. SERCA)
VOCC
Capacitative calcium entry (e.g. SOC)

Question 20

Describe the function of SOC

Answer 20

Store operated channel.

Activated by ‘depleted’ signal from the SR/ER so more calcium will enter the cell and uptake into the ER by SERCA

Question 21

What proteins interact following store depletion to activate SOC?

Answer 21

STIM - ER membrane-located calcium sensor

ORAI - plasma membrane channel