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Year 1 Intro to Pharmacology and Physiology > Calcium Regulation > Flashcards

Calcium Regulation Flashcards

1
Q

What is the concentration of extra cellular calcium?

What two forms is it found?

A

2-2.5mM is the total
Some of this is dissolved ionised Calcium ions and other parts are bound to other molecules.
The free ion concentration is 1-1.4mM

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2
Q

Which is spatiotemporal homogenous the concentration of extra cellular or intracellular calcium

A

Extra cellular

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3
Q

What is the concentration of intracellular free calcium?

A

100nM
Very low, which means small changes cause big percentage changes which is good for making calcium signalling a relatively cheap bio energetic source of messenger.

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4
Q

Where is the big store of intracellular calcium?

A

Smooth endoplasmic reticulum and in muscle cells this organelle is known as the sarcoplasmic reticulum.

Note mitochondria also have relatively small stores, but this is used as a buffer in excessive Calcium ion levels, not as a functional store.

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5
Q

What is the concentration of calcium in the SER or SR in muscle cells?

A

300microM to 1mM

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6
Q

What happens if calcium levels in the cell changes?

A

Calcium is important as a messenger so if levels aren’t controlled the reactions it activates will remain active and eventually result in cell death.

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7
Q

Why do Calcium ions cause a conformational change?

A

Calcium ions can fit in small gaps of molecules including proteins. It’s positive charge allows it to attract negatively charge parts of macromolecule like the oxygen in amino acids. The calcium can simultaneously bond with 6-8 negative charged areas of a molecule at different bond angles. This bonding causes a change in protein shape which thus alters its function: conformation.

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8
Q

What role does calcium play in metabolism?

A

Regulation of many metabolic enzymes including TCA cycle
Glycogenolysis
Lipolysis
Bone Metabolism

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9
Q

What role does calcium play in hormone regulation?

A

Formation and degradation of cyclic AMP and GMP

Triggering release of hormones

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10
Q

What are the membrane linked functions of calcium?

A

Excitation-contraction coupling
Excitation-secretion coupling eg neurotransmitter release
Action potential generation
Plasma Membrane vesicle fusion

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11
Q

Which contractile and motile systems does calcium play a part?

A

Muscle myofibrils
Cilia and flagella
Micro tubules and microfillaments
Cytoplasmic streaming

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12
Q

What functions is calcium involved in the intracellular signalling functions?

A 
Protein Kinases Proteases
Protein Phosphate (calineurin)
Production of messengers eg NO
Gene expression
Neuro Genesis memory 
Apoptosis
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13
Q

Is the concentration gradient from the extra cellular and storage SER/SR to the intracellular cytosol steep or shallow?

A

Steep

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14
Q

What is the rapid release intracellular course of calcium ions?

A

SER/SR

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15
Q

What is the no rapid release calcium store?

A

The mitochondria

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16
Q

Is the movement of calcium out of the cell an energy expensive or inexpensive activity?

A

Expensive, you are moving against the concentration gradient and thus require energy.

17
Q

Are resting cell membranes permeable or impermeable to calcium ions?

A

Impermeable

18
Q

What are the three major routes (channels) in the plasma membrane exhibit highly selective permeability to calcium ions?

A

Voltage Gated/Operated Calcium Channels (neurons)
Ligand Gated Ion Channels
Store Operated Channels

19
Q

What activates voltage gated calcium channels?

A

Cell depolarisation allows calcium to flow down the concentration gradient rapidly.
Note not all VGCC have the same maximum calcium ion capacity.

20
Q

How do Ligand gated Ion Channels work?

A

Most are activated by neurotransmitters and when. The bind to the channel it opens allowing calcium to flow into the cell.

Eg NMDA which also carries potassium and sodium ions. It carries such large calcium ion currents it can cause neuron burn out through excess calcium ions.

21
Q

Store operated channels are used to replenish which part of the bodies calcium store?

A

This channel takes calcium from the extra cellular fluid when the SER/SR store is depleted and the calcium ATPase pump has been very active.

22
Q

Are store operated channels fast flowing or slow?

A

Slow

23
Q

How is the store operated channel regulated?

A

Calcium sensing proteins in the SER. They detect if calcium in the SER is low and will oppose the SOC, this process is important in smooth muscle where prolonged stable contraction is necessary.

24
Q

How does calcium leave the cytosol into the extra cellular space?

A

Plasma membrane ATPase (PMCA)

The sodium calcium exchanger (NCX)

25
Q

Plasma Membrane calcium ATPase is found on all cells, is its affinity to calcium high or low and what can raise its affinity?

A

High affinity which can be raised by binding of calmodulin a cytoplasmic calcium sensing protein, this protein is a not common and thus fine tunes the concentration.

26
Q

How many ATP molecules are used by a plasma membrane Calcium ATPase pump to transport one calcium ion in to the cell?

A

1 ATP molecule is used.

27
Q

Is ATP used by the sodium calcium exchanger?

A

The sodium calcium exchanger is not called a pump because it does not in itself directly use ATP in stead it uses the energy gradient from the lager concentration of extra cellular sodium. It will take 3 sodium out for every one calcium ion it ejects.
The electrochemical gradients normally remain unaffected because of the action of the sodium potassium ATPase pump.

28
Q

Describe the sodium calcium exchangers affinity and capacity for calcium.

A

Low affinity but high capacity when the level is reached. Above 10 microM this is the primary calcium pump.

29
Q

Which calcium effluent protein is reversible and what causes this?

A

Highly depolarised cells where intracellular sodium is high the sodium calcium exchanger will reverse its activity.

30
Q

How do we regulate calcium from our intracellular stores?

A

GPCRs (Gq type) in the plasma membrane
IP3 receptors on the SER/SR membrane
Ryanodine Receptos in the SER/SR

31
Q

What happens when a GPCR is triggered to regulate SER/SR calcium levels?

A

Gq type receptors have suitable ligand attachment triggering production of Inositol Triphosphate from membrane phospholipids.
The IP3 diffuses a cross the cytoplasm to bind with the IP3 receptors on the membrane of the SER/SR.

32
Q

What type of channel is the IP3 receptor?

A

Ligand gated found on the external membrane face of the SER/SR.

33
Q

What role does the IP3 receptor play?

A

When appropriate ligands bind to it the channel allows effluent of calcium from SER/SR to the cytosol. The activity is proportional to the level of calcium driving IP3 production. If IP3 production falls because the calcium level in the cytosol is high enough and thus IP3 production is no longer being stimulated the IP3 receptor activity will reduce.

34
Q

What is the ligand on a Ryanodine Receptor and where is it found?

A

Calcium ions are the ligands

The receptors are on the external face of the SER/SR membrane

35
Q

Where are Ryanodine receptors found most?

A

Muscle cells, but are expressed across all cell types.

36
Q

How does the activation vary for Ryanodine receptors?

A

Smooth muscle and cardiac muscle the RyR receptors are triggered by the calcium signalling from VOCCs. Depolarisation triggers opening of VOCC, the influx of calcium opens the RyR causing a large synchronous outward flux of calcium. Calcium induced Calcium Release. CICR.

Skeletal muscle have t-tubules directly physically coupled. This tubule means as a VOCC opens so does the RyR.

37
Q

How do we get calcium from the intracellular sink back into the intracellular source (SER/SR)?

A

SERCA- Smooth/Sarco endoplasmic reticulum Calcium ATPase.
Much like PMCA but on the SER/SR membrane not the cell membrane.
Important in the external cell stimulation ending, this channel works well in conjunction with the sodium calcium exchanger. This requires energy to move calcium against the concentration gradient.

38
Q

Mitochondrial Calcium stores are most active when the cell has high or low calcium levels?

A

Very high levels, the system has low affinity but high capacity at this level.

39
Q

Controlling intracellular calcium is done by which two major protein groups?

A

Calcium buffers

Calcium Sensors/ Trigger Proteins

Year 1 Intro to Pharmacology and Physiology (8 decks)

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