ICPP 3 Intracellular pH + Cell Volume Control Flashcards
Cytoplasmic pH
7.2
Why does intracellular pH vary depending on the organelle?
pH relates to function
Normal pH range
7.35-7.45
Acidosis range
7-7.35
alkalosis range
7.45-7.8
Relationship between [H+] and pH
Change in [H+] by a factor of 2 causes a pH change of 0.3
Reasons for tight pH regulation
- 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
Intracellular pH dysregulation and tissue ischaemia
- 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
What is Dents disease characterised by?
Proximal tubule dysfunction > progressive renal failure
What is Dens disease due to?
Mutations in CLC5 (2Cl-/H+ exchanger)
Defective endocytosis due to impaired acidification
What does the electrochemical gradient favour?
Inward movement of H+
Outward movement of HCO3 -
Role of buffers
Immobilise H+
Reduced destructive effects
Insufficient on their own
3 primary buffer systems
Bicarbonate buffer system
Phosphate butter system
Proteins
Bicarbonate buffer system
CO2 + H2O <> H2CO3 <> H+ + HCO3 -
How do proteins act as buffers?
Contain many H+ binding sites
Phosphate buffer system
H+ + PO^4 2- <> H2PO^4 -
NHE meaning
Na+/H+ exchanger
How does the NHE control cell pH?
1 H+ out
Na+ in
What is NHE activated by?
Growth factors
What is NHE inhibited by?
Amiloride
How does the sodium bicarbonate chloride cotransporter control cell pH?
1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out
How does the sodium bicarbonate chloride cotransporter control cell pH?
1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out
NBC meaning
Sodium bicarbonate chloride cotransporter
How doe NBC control cell pH?
1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out
AE meaning
Anion exchanger
Cl/HCO3 - exchanger
What is the AE dependent on?
The conc of the ions its transporting
What type of transporters are NHE and NBC and what are the dependent on?
Secondary
Facilitated diffusion
Dependent on Na+ electrochemical gradient set by the Na+ K+ pump
What pH does NHE work best at?
Low pH
H+ out > alkalises cell
What pH does AE2 work better at?
High pH
Acidifies cell
Why does cell volume need to be regulated?
- Excessive swelling jeopardises membrane integrity
- Swelling and shrinking interferes with cytoskeleton
- Cell function dependent on correct protein hydration
Hypernatremic meaning
High Na+ blood conc
Hyponatremic meaning
Low Na+ blood conc
Relationship of solutes and water
- water follows solutes
- net influx of solutes > net influx of water > cell swelling
- net efflux of solutes > net efflux of water > cell shrinkage
Acid extruders
NHE - efflux of H+»_space; alkalisation of cell
Sodium bicarbonate cotransporter - coupled with Cl- > alkalisation by removing H+ and adding HCO^3 -
Base extruders
Cl-/HCO^3 - exchanger (anion exchanger) - acidifies cell
Mechanisms to resist cell swelling
- conductive systems
- cotransport systems
Efflux of osmotically active solutes K+ or Cl-»_space; water follows»_space; reduced cell swelling
regulatory volume decreases
Mechanisms to resist cell shrinking
- conductive systems
- cotransport systems
Influx of osmotically active ions Na+, K+ or Cl-»_space; water follows in»_space; reduces cell shrinking
Regulatory volume increase
NHE
SBC - sodium bicarbonate chloride cotransporter
Longer term changes to resist cell swelling
Amino acids efflux > H2O follows > reduced cell swelling
Longer term changes to resist cell shrinkage
Synthesis or transport of organic solute
e.g. sorbitol, inositol - sugars
taurine, betaine - amines
