Control Of Cytosolic Calcium (5) Flashcards Preview

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Flashcards in Control Of Cytosolic Calcium (5) Deck (13)
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What are the pros and cons of a large inward gradient of calcium?

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


How is the calcium gradient set up?

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


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

- Ca ATPase
- Na/Ca exchanger (NCX)


How does the Ca ATPase channel work?

- 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


How does the Na/Ca exchanger work?

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


How do Ca buffers work?

- 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


How are calcium levels increased and returned to basal levels?

- 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


Outline how GPCR mediated signalling occurs.

- 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


What does CICR stand for and what is its role?

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


How is calcium released in a cardiac myocyte?

- Ryanodine receptor releases Ca ~85% of total
- Voltage operated calcium channel releases other 15% from T-tubule


How is calcium reabsorbed in the cardiac myocyte?

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


How are mitochondria used as Intracellular stores of calcium?

- 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


How are calcium levels returned to basal levels?

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