Control Of Cytosolic Calcium (5)

Question 0

How is the calcium gradient set up?

Answer 0

• Relative impermeability of plasma membrane (only via ion channels)
• Dependent upon cells ability to expel Ca across plasma membrane
• Ca buffers
• Intracellular Ca stores

Question 1

What are the pros and cons of a large inward gradient of calcium?

Answer 1

• Ads: changes in calcium concentration occur rapidly with little movement of Ca
• Disads: Ca overload can lead to loss of regulation and cell death

Question 2

What is meant by the cell being dependent upon its ability to expel Ca across plasma membrane?

Answer 2

• Ca ATPase

- Na/Ca exchanger (NCX)

Question 3

How does the Ca ATPase channel work?

Answer 3

• Feedback mechanism:
• Increase in internal calcium concentration
• Ca binds to calmodulin (trigger protein)
• Calmodulin binds to Ca-ATPase
• Ca-ATPase removes Ca
• High affinity, low capacity

Question 4

How does the Na/Ca exchanger work?

Answer 4

• Na concentration is used as driving force
• Antiporter’s electrogenic
• 1Ca to 3Na (Na in)
• Low affinity, high capacity

Question 5

How do Ca buffers work?

Answer 5

• Ca diffuses more slowly than predicted from ionic/hydrated radius
• Ca buffers limit diffusion - ATP and Ca binding proteins
• Ca diffuses v.short distance before meeting a binding molecule
• Ca diffusion depends on conc of binding molecules and level of saturation

Question 6

How are calcium levels increased and returned to basal levels?

Answer 6

• Ca influx across plasma membrane: v.gated Ca channels & receptor operated Ca channels
• Ca release from rapidly releasable Intracellular stores: SERCA pump
• Non-rapidly releasable Intracellular Ca stores

Question 7

Outline how GPCR mediated signalling occurs.

Answer 7

• Stimulus (hormone/transmitter) to receptor
• Heterogenic G protein at receptor made up of alpha, beta and gamma subunits
• Beta and gamma splits from alpha to trigger ion channels to open
• Alpha subunit consists of alpha q/s/i
• Alpha q stimulates phospholipase c then IP3 channel opening to increase Intracellular levels
• Alpha s and i both stimulate anenylyl cyclase, stimulating cAMP and so protein kinase A

Question 8

What does CICR stand for and what is its role?

Answer 8

• Ca acts as agonist on ryanodine receptor in S/ER to release Ca
• Calcium Induced Calcium Release

Question 9

How is calcium released in a cardiac myocyte?

Answer 9

• Ryanodine receptor releases Ca ~85% of total

- Voltage operated calcium channel releases other 15% from T-tubule

Question 10

How is calcium reabsorbed in the cardiac myocyte?

Answer 10

• Major: SERCA channel back into SR
• Minor: NCX (Ca in, Na out)
• RyR blocked
• Ca ATPase blocked

Question 11

How are mitochondria used as Intracellular stores of calcium?

Answer 11

• Ca buffering, regulate pattern and extent of Ca signalling
• Stimulation of mitochondrial metabolism match energy demand and supply
• Role in cell death - apoptosis/altered redox potential

Question 12

How are calcium levels returned to basal levels?

Answer 12

• Termination of stimulating signal
• Ca removal
• Ca store refilling (recycling of released Ca, VOCC and or capacitative Ca entry)