L4 - Cell Homeostasis - Sodium and Calcium Flashcards
(29 cards)
What is the importance of low intracellular Na in epithelial cells?
Thick ascending limb of Henles loop function
Reabsorption of NaCl in preference to H2O
Creates the trans-epithelial osmotic gradient responsible for counter-current multiplication
Apical membrane of thick ascending limb
NaKCC channel – activity relies on inward gradient for Na due to Na/K ATPase
K channel
Basolateral membrane of thick ascending limb
Na/K ATPase – keeps low intracellular Na
K channel
Cl channel
What happens if intracellular Na is raised in epithelial cells?
NaCl reabsorption is inhibited
Trans-epithelial osmotic gradient dissipated leading to diuresis and increased NaCl in urine
What is the importance of low intracellular Na in excitable cells?
Normal conditions
- Large inwardly directed chemical and electrical gradients for Na
What happens if intracellular Na is raised in excitable cells?
Decrease in inward chemical gradient
ENa becomes +30 mV – decrease in electrical gradient
Will take longer for the potential to develop
Problems with action potential propagation and conduction
What are the basic properties of Na/K ATPase?
Creates
- Low intracellular Na
- High intracellular K
Rate of transport is a saturable function of [Na] intracellular and [K] extracellular
Rate of transport is a saturable function of [ATP] – depends on the metabolic state of the cell
What is Na/K ATPase inhibited by?
Cardiac glycosides – ouabain and digoxin
Role of Na/K ATPase in negative membrane potential
Electrogenic transport making the cell more negative
- 3+ charges out
- 2+ charges in
Accumulation of K inside the cell creates the driving force for K to leave the cell – making the cell more negative
Movement of Na into cells is only by pathways which have physiological significance because…
High energy use generating this gradient
What two areas are Na moved into cells?
Collecting ducts
Excitable cells
Collecting ducts and Na movement
Amiloride sensitive channels are on the apical membrane – pump is basolateral
This arrangement allows directional transport
Excitable cells and Na movement
Na entry produces the depolarisation leading to the action potential
The Na is recycled by the pump but an important physiological process is occurring
Model of Na/K pump action
- Binding of Na ion
- Protein phosphorylation and conformational change
- Release of Na outside of the cell
- Binding of K
- Dephosphorylation and structural changes in protein
- Conformation returns to starting conformation – exposed to the internal environment
- Release of K inside of the cell
What is the importance of Ca regulation?
Ca is an important second messenger involved in signalling pathways
E.g. Pancreatic acinar cell
Na/Ca exchanger role in keeping intracellular Ca low
Normally exchanges extracellular Na for intracellular Ca (only reversed in the heart)
- Inward Na gradient is 10 fold
- Inward Ca gradient is 10000 fold
Electrogenic – 3+ in, 1+ out
- Effect of the Na gradient is magnified - effect of 10 fold gradient cubed
Na/Ca exchanger family
Member of SLC8 gene family and the larger CaCA superfamily
In mammals three forms exist – NCX1-3
Ca ATPase role in keeping intracellular Ca low
Contains 3 cell types
Ca ATPase family
Members of the P-type ATPase family
PMCA
Plasma membrane calcium pumps
Pump Ca across the plasma membrane out of the cell
SERCA
Found on SR or ER membrane
Pump Ca out of cytoplasm into organelles which act as Ca stores
SPCA
Found on golgi apparatus
Transports Mn
Ca signalling - plasma membrane pathways - voltage operated Ca channels
Found in excitable cells
Activated by depolarisation
Ca signalling - plasma membrane pathways - receptor operated Ca channels
Found in secretory cells and never terminals
Activated by binding of an agonist e.g. NMDA receptor
