M&R 5.2 - Control of Cytosolic Ca2+ Flashcards Preview

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Flashcards in M&R 5.2 - Control of Cytosolic Ca2+ Deck (25):
1

What are the extracellular and intracellular concentrations of Ca2+ at rest?

- Extracellular = 1-2mM

- Intracellular = ~100nM

= A large inwards gradient

2

What are the advantages of a large inwards gradient of Ca2+?

- Can have a rapid change with little Ca2+

- Not a lot needs to be removed to return to basal states

3

What are the disadvantages of a large inwards gradient of Ca2+?

- Requires a lot of energy

- Leads to cell death due to overload if it can't be dealt with

4

How does the membrane contribute to the control of intracellular Ca2+?

- Relatively impermeable

- Ca2+ can only move through specific ion channels when open

5

What is the function of NCX?

- Movement of 3Na+ in: 1Ca2+ out (electrogenic antiporter) - Causes a slight depolarisation due to net movement of +1 in

- Low affinity, high capacity

- Uses gradient set up by Na+ pump

6

How does Ca2+ATPase work?

- Moves Ca2+ across the membrane against its concentration gradient using ATP hydrolysis

- Ca2+ binds to Calmodulin first

- High affinity, low capacity = removes residual Ca2+

7

What is a Ca2+ buffer?

- Diffusion limiters

- ATP
- Ca2+ binding proteins e.g. Calbindin
- Trigger proteins

8

What happens when Ca2+ binds to trigger proteins?

- Produces a conformational change

- Alters function e.g. Calmodulin, Troponin

9

What is the function of Ca2+ buffers?

- Ensures that Ca2+ doesn't move very far in the cell before binding to something

- Distance moved is proportional to concentration of binding molecules and their saturation

10

Describe how selectively altering membrane permeability raises intracellular Ca2+ levels?

- VOCC channels open due to a conformational change after depolarisation

- Ca2+ moves into the cell down its gradient

11

What is the significance of having multiple types of Ca2+ channel?

- Different types have different properties

- Ensures the system is flexible

12

Give two examples of Ionotropic receptors

- NMDA/AMPA Receptors for Glutamate

- Nicotinic Acetylcholine Receptors

13

How do ionotropic receptors raise intracellular Ca2+ levels?

- Ligand binds to the channel causing a conformational change

- If selective to Ca2+, Ca2+ moves in down chemical (and maybe electrical) gradient

14

What is the significance of the endoplasmic/sarcoplasmic reticulum in raising calcium levels?

- Rapidly releasable Ca2+ store using SERCA

- Having binding proteins inside = can hold more Ca2+ than if it was just packed therefore increasing its capacity

15

How is Ca2+ release from SER controlled?

- GPCR

- CICR

16

Describe the GPCR mechanism for Ca2+ release from the SER

- Agonist binds to GPCR = activated

- Alpha-Q subunit dissociates and stimulates Phospholipase C

- Phospholipase C cleaves PIP2 to form IP3 and DAG

- IP3 binds to lgCa2+ channels on SER membrane allowing a Ca2+ influx into cell down its gradient

17

Describe the mechanism for calcium induced calcium release (CICR)

- Ryanodine receptors are activated by Ca2+ (due to increase in intracellular levels)

- Open due to a conformational change

- Influx from stores into cardiac myocyte = excitation contraction coupling

18

Describe the location of Ryanodine receptors and the significance of this

- Next to VOCC on t-tubules

- Rapid transmission of depolarisation
- Rapid release NEXT TO contractile machinery

19

How does Na+ contribute to Ca2+ influx?

- Increase of Na+ concentration in microdomains next to plasma domains

- Reverses NCX = small Ca2+ influx

20

How is [Ca2+]in returned to normal?

- Inactivation of Na+ = less depolarised

- Causes Ca2+ channels to close and decreases [Na+]in

- NCX returns to normal direction so moves Ca2+ out of cell normally

21

What happens if [Ca2+]in doesn't return to basal levels?

- Activates potent enzymes within the cell

- Causes cell death due to hypoxic injury

22

How are Ca2+ stores refilled?

- Recycled in cardiac myocytes

- VOCC/Capacitative Ca2+ entry = store empties so signal is sent to store operated channel = influx

23

What is the significance of capacitative entry?

Regulation of physiological processes e.g. secretion

24

What happens if the stores aren't refilled?

- Decreases contraction

- Demand of CICR can't be met

25

What is the role of non-rapidly releasable stores?

- Uptake of Ca2+ when [Ca2+]in is high (protective)

- Alters signalling
- Stimulates metabolism to match demand and energy supply

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