L4 - Cell Homeostasis - Sodium and Calcium

Question 1

What is the importance of low intracellular Na in epithelial cells?

Answer 1

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

Question 2

Apical membrane of thick ascending limb

Answer 2

NaKCC channel – activity relies on inward gradient for Na due to Na/K ATPase
K channel

Question 3

Basolateral membrane of thick ascending limb

Answer 3

Na/K ATPase – keeps low intracellular Na
K channel
Cl channel

Question 4

What happens if intracellular Na is raised in epithelial cells?

Answer 4

NaCl reabsorption is inhibited

Trans-epithelial osmotic gradient dissipated leading to diuresis and increased NaCl in urine

Question 5

What is the importance of low intracellular Na in excitable cells?

Answer 5

Normal conditions

- Large inwardly directed chemical and electrical gradients for Na

Question 6

What happens if intracellular Na is raised in excitable cells?

Answer 6

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

Question 7

What are the basic properties of Na/K ATPase?

Answer 7

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

Question 8

What is Na/K ATPase inhibited by?

Answer 8

Cardiac glycosides – ouabain and digoxin

Question 9

Role of Na/K ATPase in negative membrane potential

Answer 9

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

Question 10

Movement of Na into cells is only by pathways which have physiological significance because…

Answer 10

High energy use generating this gradient

Question 11

What two areas are Na moved into cells?

Answer 11

Collecting ducts

Excitable cells

Question 12

Collecting ducts and Na movement

Answer 12

Amiloride sensitive channels are on the apical membrane – pump is basolateral
This arrangement allows directional transport

Question 13

Excitable cells and Na movement

Answer 13

Na entry produces the depolarisation leading to the action potential
The Na is recycled by the pump but an important physiological process is occurring

Question 14

Model of Na/K pump action

Answer 14

1. Binding of Na ion
2. Protein phosphorylation and conformational change
3. Release of Na outside of the cell
4. Binding of K
5. Dephosphorylation and structural changes in protein
6. Conformation returns to starting conformation – exposed to the internal environment
7. Release of K inside of the cell

Question 15

What is the importance of Ca regulation?

Answer 15

Ca is an important second messenger involved in signalling pathways
E.g. Pancreatic acinar cell

Question 16

Na/Ca exchanger role in keeping intracellular Ca low

Answer 16

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

Question 17

Na/Ca exchanger family

Answer 17

Member of SLC8 gene family and the larger CaCA superfamily

In mammals three forms exist – NCX1-3

Question 18

Ca ATPase role in keeping intracellular Ca low

Answer 18

Contains 3 cell types

Question 19

Ca ATPase family

Answer 19

 Members of the P-type ATPase family

Question 20

PMCA

Answer 20

Plasma membrane calcium pumps

Pump Ca across the plasma membrane out of the cell

Question 21

SERCA

Answer 21

Found on SR or ER membrane

Pump Ca out of cytoplasm into organelles which act as Ca stores

Question 22

SPCA

Answer 22

Found on golgi apparatus

Transports Mn

Question 23

Ca signalling - plasma membrane pathways - voltage operated Ca channels

Answer 23

Found in excitable cells

Activated by depolarisation

Question 24

Ca signalling - plasma membrane pathways - receptor operated Ca channels

Answer 24

Found in secretory cells and never terminals

Activated by binding of an agonist e.g. NMDA receptor

Question 25

Ca signalling - plasma membrane pathways - mechanically activated Ca channels

Answer 25

Found in many cells

Respond to cell deformation

Question 26

Ca signalling - plasma membrane pathways - store operated Ca channels

Answer 26

Activated following depletion of Ca stores

Question 27

Ca signalling - store pathways - IP3 receptors

Answer 27

Activated following binding of IP3

Found in most cell types

Question 28

Ca signalling - store pathways - ryanodine receptors

Answer 28

Activated by low concentration of ryanodine
Inhibited by higher concentrations
Also stimulated by caffeine
Found in excitable cells

Question 29

Store operated calcium channel activation method

Answer 29

1. Activated receptor
2. Activated PLC and PIP2
3. PIP2 activated DAG and IP3
4. IP3 stimulates the release of Ca from stores inside the cell
5. If these are depleted a signal is sent to the SOCC
6. This then stimulates release of Ca from SOCC in the membrane