ATP-dependent Pumps and Ion Exchangers Flashcards

1
Q

Give examples of ion transports.

A
Na+K+ATPase
SERCA
PMCA (plasma membrane calcium ATPase)
NCX (Calcium sodium exchanger)
NHE (Sodium hydrogen exchanger)
AE (anion exchange)
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2
Q

What are the functions of Na+K+ATPase?

A

Necessary for electrical excitability however it only contributes about 5mV to resting membrane potential
It also drives secondary transport like NCX, NHE and absorption of Na+ in epithelia. It also drives glucose and amino acid uptake in small intestine.
It is very important in order to keep the calcium gradient that is.

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3
Q

Why is the concentration of calcium so small in the cell?

A

Because a small change in the concentration would lead to a big difference.
Also calcium would bind to phosphate rendering phosphate useless.

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4
Q

What lowers/regulates the intracellular (cytoplasmic) concentration of calcium?

A

Na+K+ATPase plays and important role.
NCX exchanges sodium and calcium. Calcium leaves.
PMCA uses ATP to pump out calcium.
SERCA uses ATP to pump in calcium into ER or SR
Also there are mitochondrial Ca2+ uniports where mitochondria takes up Ca2+. The mitochondrial uniport is used if calcium reaches a toxic level.

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5
Q

What are the functions of the sodium calcium exchanger (NCX)?

A

It exchanges 1 Ca2+ for 3 Na+. This means that the intracellular environment gets a little bit more positive.
It expels Ca2+ from the cytoplasm which is very important.
Possibly important in cell toxicity during ischaemia/reperfusion.

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6
Q

What does the NCX depend on?

A

It is membrane potential dependent.

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7
Q

What happens in a polarised cell to the NCX?

A

This means that the intracellular environment is negative compared to the outside. Sodium goes into the cell and calcium goes out.

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8
Q

What happens in a depolarised cell to the NCX?

A

This means that the intracellular environment is positive compared to the outside. Sodium goes out of the cell and calcium goes in. This means that it is dependent on the membrane potential.

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9
Q

Why would the NCX let calcium go in during depolarisation?

A

Because depolarisation happens during an action potential. For example in the cardiac muscle when an action potential is conducted you want the heart to contract and beat. This means that calcium needs to enter the cell.

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10
Q

How does the NCX relate to ischaemia?

A

Blood doesn’t reach a limb. Glucose gets lower there and ATP is depleted. This means that the Na+K+ATPase won’t work properly. Na+ accumulates inside the cell because of this and the cell depolarises. Due to the depolarisation calcium will enter the cell and build up to a toxic level which can lead to cell death.

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11
Q

How is the cell’s pH controlled?

A

By acid extruders and base extruders.

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12
Q

Give examples of acid extruders.

A

NHE which is a NA+/H+ exchanger where Na+ goes in and H+ goes out. This increases the pH of the cell.
Na+ dependent CL-/HCO3- exchanger also called NBC (sodium bicarbonate cotransporter)
It works as an antiport and symport. Sodium and bicarbonate enters the cell whereas H+ and Cl- leaves the cell.

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13
Q

Give an example of a base extruder.

A

Cl-/HCO3- exchanger Anion exchanger. (AE) HCO3- is transported out and Cl- is transported in.

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14
Q

Give features of the NHE.

A

Na+ goes in and H+ goes out. It is electroneutral and regulates the intracellular pH.
It regulates cell volume.

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15
Q

What is NHE activated by?

A

Growth factors

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16
Q

What is NHE inhibited by?

A

Amiloride

17
Q

What makes the acid extruders working?

A

The Na+K+ATPase.

18
Q

How is the cell volume regulated?

A

By the NHE, NBC and AE.

When osmotically active ions like Na+, K+ and Cl- are transported either in or out of the cell water will follow.

19
Q

What happens regarding to cell volume if there is an influx of Na+?

A

Water follows and the cell swells.

20
Q

What happens regarding to cell volume if there is an efflux of Na+?

A

Water follows and the cell shrinks.

21
Q

If a cell is swelling up what will happen?

A

NHE, NBC and AE will work together to extrude ions to make the cell shrink again. These work without changing membrane potential!
K+, Cl and Na+ will be extruded from the cell.

22
Q

If a cell is shrinking what will happen?

A

Na+, K+ and Cl- will enter the cell.

23
Q

What role does bicarbonate have in transport?

A

It’s used in the NBC as an acid extruder and in AE (Cl-/HCO3- exchange) as a base extruder. It is also important in cell volume regulation.
Bicarbonate reabsorption is used in the proximal tubule as well in order to retain base for pH buffers.

24
Q

How can hypertension be treated by ion transport?

A

Renal control of circulating Na+ concentration is used often as a first line treatment for mild hypertension. Hypertension is caused from too much water in the blood system. So we need to remove water.

25
Q

How can regulation of Na+ by the kidneys be used clinically?

A

Na+ reuptake by the kidney is important in order to treat hypertension.

26
Q

How is Na+ concentration regulated in the thick ascending limb?

A

By inhibiting NKCC2, a transporter which would make sodium go out in the blood stream. Inhibiting this will prevent Na+ to get taken up in the blood stream and because of that also preventing water to follow and cause more hypertension. Instead water goes into the kidney and relives the hypertension.

27
Q

How is Na+ concentration regulated in the distal convoluted tubule?

A

Thiazides and amiloride will inhibit NCCT and Enac or NHE respectively. This prevents sodium from being taken up by the blood and will instead stay in the kidney.

28
Q

How does aldosterone work?

A

It promotes reabsorption of Na+ and therefore also water into the blood stream. This can cause hypertension.

29
Q

How is aldosterone inhibited?

A

By spironolactone which blocks aldosterone from working and therefore lowers blood pressure.