ICPP 5 - Primary & Secondary AT's (Part 2)

Question 1

What are the 2 main functions of the Na/K ATPase?

Answer 1

1) Form Na and K gradients - for electrical excitability
2) Drive secondary AT - for control of pH, cell volume, IC Ca2, absorption of Na+ in epithelia and glucose uptake from SI.

Question 2

Why are intracellular levels of Ca2+ extremely small? (compared to EC concentration)

Answer 2

Phosphate is a key pH buffer within the cell, however calcium phosphate forms a precipitate would be toxic to cells.

Question 3

What are the 5 transporters that control the levels of resting intracellular calcium?

Answer 3

1) Na/K ATPase (primary AT)
2) NCX (secondary AT)
3) PM Ca2+ ATPase (primary AT)
4) SERCA (primary AT)
5) Ca2+ uniporters (facilitated transport)

Question 4

What is the role of the Na-Ca exchanger?

Answer 4

To take in 3 x Na+ molecules for every 1 x Ca2+ ion it removes. Plays a role in expelling IC Ca2+ during cell recovery and cell toxicity during ischaemia.

Question 5

What is the direction of the NCX dependent on?

Answer 5

It is dependent on the membrane potential:
Cell polarised = low IC Na+ so it works normally
Cell depolarised = High IC Na+ so it reverses and brings in calcium (responsible for plateau in cardiac AP).

Question 6

How does the NCX contribute to cell toxicity during ischaemia?

Answer 6

• Low O2 so ATP synthesis via oxidative phosphorylation is depleted
• Not enough ATP for Na/K pump to extrude Na+
• Na+ accumulated within cell, causing NCX to flip into reverse mode
• Calcium brought into the cell leading to cell toxicity

Question 7

What are the 2 acid extruders and 1 base extruder that control cell pH?

Answer 7

Acid extruders:
- Na/H exchanger (NHE)
- Na+ dependent Cl-/HCO3- exchanger (NBC)
Base extruders:
- Cl-/HCO3- extruder (AE)

Question 8

Therefore, what are the 5 ion transporters that regulate cellular pH?

Answer 8

1) Na/K+ ATPase (provides Na+ gradient for energy for the other 4 transporters)
2) Na/H exchanger (NHE)
3) NBC
4) AE
5) Na-HCO3- co-transporter

Question 9

Which ion channels are activated when intracellular pH moves either side of the set point?

Answer 9

Acidification = NHE + NBC activated
Alkalisation = AE activated

Question 10

How is cell volume regulated via transporters?

Answer 10

Cell swelling = Extrude ions (e.g.: conductive systems such as K + Cl- ion channels or co-transport systems such as KCl- co-transporter)
Cell shrinkage = Influx ions (vice versa but with Na and Ca2+)