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BIO304 > Module 5.1 - Calcium Transport Mechanisms > Flashcards

Module 5.1 - Calcium Transport Mechanisms Flashcards

1
Q

Why is cytoplasmic calcium good?

A

Binds oxygen atoms
Causes conformational changes in proteins

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2
Q

Why is it good that cytoplasmic calcium binds O atoms?

A

Can bind to carboxyl and carbonyl groups on amino acids

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3
Q

Why is it good that cytoplasmic calcium causes conformational changes in proteins?

A

Good for signaling or activating mechanical processes

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4
Q

Give examples of mechanical processes that cytoplasmic calcium can contribute to (6)

A

Vesicle exocytosis
Muscle contraction
Activating other ion channels
Changes in gene expression
Apoptosis
Intracellular signaling

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5
Q

Why is cytoplasmic calcium bad?

A

Precipitates phosphates
Can trigger apoptosis
Cannot be chemically altered for neutralization

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6
Q

Why is it bad for cytoplasmic calcium to precipitate phosphates?

A

Can accumulate and become toxic

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7
Q

What is the general [Ca]in? [Ca]out? How large is this difference?

A

In: 0.001mM
Out: 1 mM
10,000 fold difference

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8
Q

What is the difference in cytoplasmic K+ and Ca2+?

A

1,500,000 fold

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9
Q

When does cytoplasmic calcium concentration increase transiently?

A

During neuronal excitation and muscle contraction

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10
Q

Give a pathological example of an increase in cytoplasmic calcium.

A

After a stroke: positive feedback triggers increase

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11
Q

Outline the sequence of damaging events in a stroke. (5)

A
  1. Blood clot stops the flow of blood to a brain region
  2. Without oxygen and glucose, neurons begin to depolarize, perhaps due to loss of ATP causing loss of K+/Na+ pump. Neurons reach threshold and produce barrage of APs
  3. Many of these rapidly firing neurons release glutamate (excitatory nt). Plus, lack of energy in presynaptic neuron prevents glutamate receptors from working (no reuptake).
  4. Glutamate bombards postsynaptic neurons, causing barrage of APs, possibly spreading glutamate flood and leading to excess Ca and Zn entering cell
  5. Excess Ca and Zn trigger apoptosis, neuron succumbs to excitotoxicity.
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12
Q

How do cells remove cytoplasmic Ca?

A

Cytoplasmic chelators/buffers bind free Ca to remove it from solution
Pumps and exchangers extrude Ca to cell exterior or intracellular compartments

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13
Q

What intracellular compartments may Ca be sent to?

A

Sarco/endoplasmic reticulum
Mitochondria

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14
Q

What are the two types of calcium pumps?

A

PMCA - Plasma membrane calcium ATPase
SERCA - Sarcoplasmic/endoplasmic reticulum calcium ATPase

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15
Q

How are PMCA and SERCA related to the Na-K ATPase?

A

P-type, thus consume ATP

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16
Q

How are SERCA and PMCA different from the Na-K ATPase?

A

Do not need a beta subunit

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17
Q

How many calcium ions are pumped out of the cell per PMCA cycle? How many ATP molecules are hydrolyzed?

A

1 ion
Hydrolysis of single ATP molecule

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18
Q

How many PMCA alpha genes do humans have?

A

4

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19
Q

Outline the 4 alpha PMCA genes.

A

alpha 1 - Brain/ubiquitous
alpha 2 - Brain and muscle
alpha 3 - brain and muscle
alpha 4 - Broad distribution

20
Q

What does a mutation of the PMCA alpha 1 gene contribute to?

A

Lethal

21
Q

What does a mutation of the PMCA alpha 2 gene contribute to?

A

Hearing loss and balance

22
Q

What does a mutation of the PMCA alpha 4 gene contribute to?

A

Male infertility

23
Q

What is the sarcoplasmic reticulum?

A

ER of muscle cells

24
Q

How many calcium ions are pumped out per SERCA cycle? How many ATP molecules are hydrolyzed?

A

2 ions
Hydrolysis of single ATP molecule

25
Q

How many SERCA alpha genes do humans have?

A

3

26
Q

Outline the three SERCA alpha genes.

A

alpha 1 - muscle contraction
alpha 2 - muscle contraction, neurons
alpha 3 - non-muscle but expressed in cardiomyocytes

27
Q

Describe the expression of SERCA in the ER/SR.

A

Highly expressed in SR to ensure efficient removal of cytoplasmic calcium and restoration of SR Ca stores.

28
Q

Describe the expression of PMCA in the cell membrane.

A

Sparsely expressed at cell membrane, only good at maintaining low cytoplasmic Ca levels when neurons not highly active

29
Q

What moves calcium much more quickly than SERCA/PMCA?

A

Ion exchangers

30
Q

What is the type of transport performed by calcium ion exchangers?

A

Secondary active transport

31
Q

Explain how calcium ion exchangers work and how this defines them as secondary active transporters.

A

Do not hydrolyze ATP
Consume energy from existing ion concentration gradients in exchange for moving desired ions against their concentration gradients.

32
Q

What exchanger uses the Na gradient?

A

NCX - Na Ca exchanger

33
Q

What is another name for NCX?

A

Sodium-calcium antiporter

34
Q

How is NCX able to depolarize Vm?

A

1 Ca out for 3 Na in

35
Q

What is the most widely distributed sodium-calcium exchanger?

A

NCX

36
Q

How does NCX operate in reverse?

A

Whichever ion type (Ca or Na) experiences strongest inward pull wins. Determined by net ion charge x DF

37
Q

What exchanger is better at removing cytosolic Ca than NCX?

A

NCKX

38
Q

What is NCKX?

A

Na-Ca-K exchanger. uses sodium and potassium grdients

39
Q

Describe the ion exchange of NCKX.

A

4 sodium in and 1 potassium out for every calcium out

40
Q

How many transmembrane segments does NCX have?

A

9

41
Q

How many NCX genes do humans have and where are they expressed?

A

3
1 in muscle
2 and 3 in brain

42
Q

How many transmembrane segments does NCKX have?

A

11

43
Q

What terminus of NCKX is cleaved?

A

N-T

44
Q

How many NCKX genes do mammals have?

A

5

45
Q

Where are each of the NCKX genes expressed?

A

1 - retina
2 - retina and brain
3 and 4 - brain and smooth muscle
5 - not expressed at membrane

46
Q

What is NCKX5 polymorphism associated with?

A

White skin in individuals in Europe and Asia

47
Q

What is a possible function of the NCKX5 gene?

A

Calcium regulation in melanosomes

BIO304 (13 decks)

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