ICPP 3 Intracellular pH + Cell Volume Control

Question 1

Cytoplasmic pH

Answer 1

7.2

Question 2

Why does intracellular pH vary depending on the organelle?

Answer 2

pH relates to function

Question 3

Normal pH range

Answer 3

7.35-7.45

Question 4

Acidosis range

Answer 4

7-7.35

Question 5

alkalosis range

Answer 5

7.45-7.8

Question 6

Relationship between [H+] and pH

Answer 6

Change in [H+] by a factor of 2 causes a pH change of 0.3

Question 7

Reasons for tight pH regulation

Answer 7

• disrupts electrostatic interaction + H bonding
  (doesn’t effect covalent)
• alters protein structure and function
• alters binding of substrate and ligands
• alters net electrical charge on proteins

Question 8

Intracellular pH dysregulation and tissue ischaemia

Answer 8

• Reduced blood flow > reduced O2 supply > anaerobic glycolysis > lactic acid > cytoplasmic acidification
• overactivation of NHE > intracellular Na overload > Ca overload via NCE
• leads to altered cellular function, apoptosis + necrosis

Question 9

What is Dents disease characterised by?

Answer 9

Proximal tubule dysfunction > progressive renal failure

Question 10

What is Dens disease due to?

Answer 10

Mutations in CLC5 (2Cl-/H+ exchanger)
Defective endocytosis due to impaired acidification

Question 11

What does the electrochemical gradient favour?

Answer 11

Inward movement of H+
Outward movement of HCO3 -

Question 12

Role of buffers

Answer 12

Immobilise H+
Reduced destructive effects
Insufficient on their own

Question 13

3 primary buffer systems

Answer 13

Bicarbonate buffer system
Phosphate butter system
Proteins

Question 14

Bicarbonate buffer system

Answer 14

CO2 + H2O <> H2CO3 <> H+ + HCO3 -

Question 15

How do proteins act as buffers?

Answer 15

Contain many H+ binding sites

Question 16

Phosphate buffer system

Answer 16

H+ + PO^4 2- <> H2PO^4 -

Question 17

NHE meaning

Answer 17

Na+/H+ exchanger

Question 18

How does the NHE control cell pH?

Answer 18

1 H+ out
Na+ in

Question 19

What is NHE activated by?

Answer 19

Growth factors

Question 20

What is NHE inhibited by?

Answer 20

Amiloride

Question 21

How does the sodium bicarbonate chloride cotransporter control cell pH?

Answer 21

1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out

Question 22

How does the sodium bicarbonate chloride cotransporter control cell pH?

Answer 22

1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out

Question 23

NBC meaning

Answer 23

Sodium bicarbonate chloride cotransporter

Question 24

How doe NBC control cell pH?

Answer 24

1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out

Question 25

AE meaning

Answer 25

Anion exchanger Cl/HCO3 - exchanger

Question 26

What is the AE dependent on?

Answer 26

The conc of the ions its transporting

Question 27

What type of transporters are NHE and NBC and what are the dependent on?

Answer 27

Secondary Facilitated diffusion Dependent on Na+ electrochemical gradient set by the Na+ K+ pump

Question 28

What pH does NHE work best at?

Answer 28

Low pH H+ out > alkalises cell

Question 29

What pH does AE2 work better at?

Answer 29

High pH Acidifies cell

Question 30

Why does cell volume need to be regulated?

Answer 30

- Excessive swelling jeopardises membrane integrity - Swelling and shrinking interferes with cytoskeleton - Cell function dependent on correct protein hydration

Question 31

Hypernatremic meaning

Answer 31

High Na+ blood conc

Question 32

Hyponatremic meaning

Answer 32

Low Na+ blood conc

Question 33

Relationship of solutes and water

Answer 33

- water follows solutes - net influx of solutes > net influx of water > cell swelling - net efflux of solutes > net efflux of water > cell shrinkage

Question 34

Acid extruders

Answer 34

**NHE** - efflux of H+ >> alkalisation of cell **Sodium bicarbonate cotransporter** - coupled with Cl- > alkalisation by removing H+ and adding HCO^3 -

Question 35

Base extruders

Answer 35

**Cl-/HCO^3 - exchanger** (anion exchanger) - acidifies cell

Question 36

Mechanisms to resist cell swelling

Answer 36

- **conductive systems** - **cotransport systems** Efflux of osmotically active solutes *K+ or Cl-* >> water follows >> reduced cell swelling **regulatory volume decreases**

Question 37

Mechanisms to resist cell shrinking

Answer 37

- **conductive systems** - **cotransport systems** Influx of osmotically active ions *Na+, K+ or Cl-* >> water follows in >> reduces cell shrinking **Regulatory volume increase** *NHE* *SBC* - sodium bicarbonate chloride cotransporter

Question 38

Longer term changes to resist cell swelling

Answer 38

Amino acids efflux > H2O follows > reduced cell swelling

Question 39

Longer term changes to resist cell shrinkage

Answer 39

Synthesis or transport of organic solute *e.g. sorbitol, inositol - sugars taurine, betaine - amines*