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ESA 2 > M&R 5.2 - Control of Cytosolic Ca2+ > Flashcards

M&R 5.2 - Control of Cytosolic Ca2+ Flashcards

1
Q

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

A
  • Extracellular = 1-2mM
  • Intracellular = ~100nM

= A large inwards gradient

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2
Q

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

A
  • Can have a rapid change with little Ca2+

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

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3
Q

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

A
  • Requires a lot of energy

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

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4
Q

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

A
  • Relatively impermeable

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

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5
Q

What is the function of NCX?

A
  • 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
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6
Q

How does Ca2+ATPase work?

A
  • Moves Ca2+ across the membrane against its concentration gradient using ATP hydrolysis
  • Ca2+ binds to Calmodulin first
  • High affinity, low capacity = removes residual Ca2+
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7
Q

What is a Ca2+ buffer?

A
  • Diffusion limiters
  • ATP
  • Ca2+ binding proteins e.g. Calbindin
  • Trigger proteins
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8
Q

What happens when Ca2+ binds to trigger proteins?

A
  • Produces a conformational change

- Alters function e.g. Calmodulin, Troponin

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9
Q

What is the function of Ca2+ buffers?

A
  • 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
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10
Q

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

A
  • VOCC channels open due to a conformational change after depolarisation
  • Ca2+ moves into the cell down its gradient
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11
Q

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

A
  • Different types have different properties

- Ensures the system is flexible

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12
Q

Give two examples of Ionotropic receptors

A
  • NMDA/AMPA Receptors for Glutamate

- Nicotinic Acetylcholine Receptors

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13
Q

How do ionotropic receptors raise intracellular Ca2+ levels?

A
  • Ligand binds to the channel causing a conformational change
  • If selective to Ca2+, Ca2+ moves in down chemical (and maybe electrical) gradient
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14
Q

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

A
  • Rapidly releasable Ca2+ store using SERCA

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

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15
Q

How is Ca2+ release from SER controlled?

A
  • GPCR

- CICR

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16
Q

Describe the GPCR mechanism for Ca2+ release from the SER

A
  • 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
Q

Describe the mechanism for calcium induced calcium release (CICR)

A
  • 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
Q

Describe the location of Ryanodine receptors and the significance of this

A
  • Next to VOCC on t-tubules
  • Rapid transmission of depolarisation
  • Rapid release NEXT TO contractile machinery
19
Q

How does Na+ contribute to Ca2+ influx?

A
  • Increase of Na+ concentration in microdomains next to plasma domains
  • Reverses NCX = small Ca2+ influx
20
Q

How is [Ca2+]in returned to normal?

A
  • 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
Q

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

A
  • Activates potent enzymes within the cell

- Causes cell death due to hypoxic injury

22
Q

How are Ca2+ stores refilled?

A
  • Recycled in cardiac myocytes

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

23
Q

What is the significance of capacitative entry?

A

Regulation of physiological processes e.g. secretion

24
Q

What happens if the stores aren’t refilled?

A
  • Decreases contraction

- Demand of CICR can’t be met

25
Q

What is the role of non-rapidly releasable stores?

A
  • Uptake of Ca2+ when [Ca2+]in is high (protective)
  • Alters signalling
  • Stimulates metabolism to match demand and energy supply

ESA 2 (63 decks)

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