ATP Dependent Pumps and Ion Exchangers

Question 1

What are the functions of the Na pump?

Answer 1

1) Forms Na+ and K+ gradients but only contributes abut -5mV to the resting membrane potential. Main contributor is efflux of potassium ions
2) Drives secondary active transport

Question 2

What are some examples of the Na pump driving secondary transport?

Answer 2

Control of intracellular pH
Regulation of cell volume
Regulation of intracellular calcium concentration
Absorption of Na+ in epithelia
Nutrient uptake eg glucose in the small intenstine

Question 3

What is intracellular [Ca2+] and what is extracellular [Ca2+]?

Answer 3

Intracellular = 100nM (or 0.1 micromoles or 0.0001 millimoles)

Extracellular = 1-2mM

Question 4

In which tissues would extracellular calcium levels be at the higher end of 1-2mM?

Answer 4

Eg bone

Question 5

In which tissues would extracellular calcium levels be at the lower end of 1-2mM?

Answer 5

Eg muscle

Question 6

What is the difference in calcium levels across the plasma membrane?

Answer 6

10,000 to 20,000 fold

Question 7

As cells are signalled by small changes in intracellular [Ca2+], roughly how much is needed to signal?

Answer 7

About 20nM

Question 8

Is PMCA a primary or secondary transporter?

Answer 8

Primary active transporter

Question 9

Why isn’t SERCA a pump?

Answer 9

It is not on the plasma membrane

Question 10

Where is an example of Ca2+ uniporters?

Answer 10

Ca2+ being transported into the mitochondria (Mitochondrial calcium uniporter)

Question 11

When do mitochondrial calcium uniporters operate?

Answer 11

At high intracellular calcium levels to buffer potentially damaging [Ca2+]

Question 12

What are the two primary active transporters involved in control of resting [Ca2+]i?

Answer 12

PMCA (expels Ca2+ out of the cell)

SERCA (accumulates Ca2+ into SR/ER)

Question 13

What is the affinity compared to the capacity of both PMCA and SERCA?

Answer 13

High affinity, low capacity

Question 14

What is the secondary active transporter involved in control of resting [Ca2+]i?

Answer 14

NCX

Question 15

What is the affinity compared to the capacity of NCX?

Answer 15

Low affinity, high capapcity

Question 16

What is the role of NCX?

Answer 16

Expels intracellular Ca2+ during cell recovery by exchanging 3 Na+ for 1 Ca2+

Question 17

What is meant by the electrogenic nature of NCX?

Answer 17

Current flows in the direction of the Na+ gradient.

Question 18

If the cell is depolarised, which way does NCX function?

Answer 18

Moves 1 Ca2+ in for 3Na+ out

Question 19

What happens to the NCX in ischaemia?

Answer 19

ATP is depleted so the sodium pump is inhibited, leading to the accumulation of sodium ions inside the cell and causing the cell to be depolarised. The NCX therefore reverses and moves one calcium ion in for every three sodium ions out. High intracellular calcium levels are toxic.

Question 20

What exchangers are involved in control of cell pH?

Answer 20

Na+/H+ exchanger (NHE)
Cl-/HCO3- exchanger
NBC (sodium bicarbonate cotransporter)
Anion exchanger

Question 21

What does the Na+/H+ exchanger do?

Answer 21

Exchanges extracellular Na+ for intracellular H+
Electroneutral 1:1 exchange
Regulates pH intracellularly and cell volume

Question 22

What is NHE inhibited by?

Answer 22

Amiloride (a potassium sparing diuretic - stops potassium entering urine)

Question 23

What transporter alkalinises the cell?

Answer 23

Na+-bicarbonate-chloride cotransporter (NBC)

Question 24

What transporter acidifies the cell?

Answer 24

Anion exchanger (AE1) Band 3 - moves HCO3- out and Cl- in. Also holds shape of erythrocytes.

Question 25

How does the cell respond to shrinking?

Answer 25

Influx of ions so that water will enter the cell

Question 26

How does the cell respond to swelling?

Answer 26

Extrusion of ions so that water leaves the cell

Question 27

How does the kidney reabsorb all of the sodium bicarbonate filtered into the proximal tubule?

Answer 27

NHE pumps sodium ions out of the lumen of the proximal tube and into the epithelial cell and pumps H+ ions into the lumen. The sodium then enters the capillary via the Na pump. H+ ions pumped into the lumen of the proximal tube combine with bicarbonate ions to make carbonic acid which is acted upon by carbonic anhydrase to form water and carbon dioxide. Water and carbon dioxide can freely pass through the membrane into the cell. Another carbonic anhydrase then converts the water and carbon dioxide back into carbonic acid in the cell which dissociates into H+ and bicarbonate ions. The bicarbonate ions are then transported into the capillary via an anion exchanger. The H+ ions can then be reused in NHE, which drives the process.

Question 28

Why do you need bicarbonate ions?

Answer 28

Buffering capacity in blood

Question 29

How do loop diuretics work in treating mild hypertension?

Answer 29

Act on the Na+-K+-2Cl- symporter in the thick ascending limb to inhibit reabsorption of sodium, chloride and potassium ions which will stay in the lumen of the tube. Therefore the ions do not leave and water does not follow so blood pressure is controlled

Question 30

What is an example of a loop diuretic?

Answer 30

Furosemide

Question 31

What do thiazides do?

Answer 31

Inhibit reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter

Question 32

When are thiazides often used?

Answer 32

People with type 2 diabetes

Question 33

What does Amiloride inhibit?

Answer 33

Epithelial sodium co-transporter (ENaC) thereby inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron.

Question 34

What does antidiuretic hormone stimulate?

Answer 34

Production of aquaporins

Question 35

What does alcohol do to antidiuretic hormones?

Answer 35

Stops the production of antidiuretic hormone so aquaporins are not produced and water is not being reabsorbed into the body so a lot of urine is produced

Question 36

What is Spironolactone?

Answer 36

Mineralocorticoid receptor antagonist - used in people with high levels of hypertension