L4 - Cell Homeostasis

Question 1

Normal Na IC

Answer 1

10-15 mM

Question 2

Normal Na EC

Answer 2

145-150 mM

Question 3

Why must Na levels be carefully controlled

Answer 3

To drive other secondary active processes inside of the cell

Question 4

Give an example of a secondary active process in the cell which relies on the Na gradient

Answer 4

NHE

Question 5

What process is NHE involved in

Answer 5

Acid extrusion

Question 6

What is the function of the thick ascending limb

Answer 6

To absorb Na and Cl in preference of water. NKCC2 cotransporter relies on the inward gradient for Na movement to couple inward movement of Cl (x2) and K.

Question 7

What is the transepithelial osmotic gradient responsible for

Answer 7

Counter current multipllication

Question 8

If IC Na levels were high in the TAL what would happen?

Answer 8

NaCl reabsorption would be inhibited

Transepithelial osmotic gradient is dissipated

Question 9

Ena

Answer 9

+60 mV

Question 10

Ek

Answer 10

-70/80 mV

Question 11

Vm resting

Answer 11

-70 mV

Question 12

In all cells there is a ____________________________ for Na

Answer 12

Chemical and electrical gradient

Question 13

In an electrically excitable cell what would be the effects of increased IC Na

Answer 13

Decrease in inward gradient for Na
Ena would drop
Electrical driving force for Na influx decreases
Takes longer for action potentials to develop
Peak of action potential lower
Slower conductance of action potentials

Question 14

Sum up the Na/K ATPase

Answer 14

3 NA OUT
2 K IN
USING ATP HYDROLYSIS

Question 15

Model of action of the Na/K ATPase

Answer 15

Na binds to cleft on pump 
Hydrolysis of ATP
Phosphoylation of pump
Conformational change - binding cleft exposed to the extracellular side of the cell
K binds to binding domain 
Dephosphorylation
Conformational change - binding domain exposed to thee intracellular environment 
K released inside of the cell

Question 16

What can be said about the rate of the Na/K ATPase

Answer 16

It is a saturable function of Na i and K o

Question 17

What does a saturable function mean

Answer 17

It will plateau and saturate when working at its max rate

Question 18

What also does the Na/K ATPase rely on

Answer 18

ATP

Question 19

The dependence on ATP makes the rate of the Na/K ATPase also a

Answer 19

Saturable function of [ATP]

Question 20

What type of drug inhibits the Na/K ATPase

Answer 20

Cardiac glycosides

Question 21

Give some examples of cardiac glycosides that inhibit the Na/K ATPase

Answer 21

Ouabaine

Digoxin

Question 22

What does the Na/K ATPase maintain

Answer 22

High Na i

Low Na o

Question 23

What are the two roles the Na/K ATPase plays in Vm determination

Answer 23

MINOR and MAJOR

Question 24

What is the MINOR role of Na/K ATPase in Vm det.

Answer 24

It is electrogenic - net loss of + from the cell

Question 25

What is the MAJOR role of Na/K ATPase in Vm det.

Answer 25

Sets up a high K IC and low K EC Leak current is the driving force for K out of the cell Vm --> Ek

Question 26

Normal Ca IC

Answer 26

1 mM

Question 27

1 mM to nM

Answer 27

1x 10^6

Question 28

Normal Ca EC

Answer 28

100 nM

Question 29

Roles of Ca inside of cells

Answer 29

Second messenger Fusion of vesicles to the membrane Contraction of muscles

Question 30

What is the difference between Ca IC and Ca EC

Answer 30

1000 times difference

Question 31

This huge Ca gradient means

Answer 31

Favours Ca influx

Question 32

E CA

Answer 32

+120 mV

Question 33

Descibe the Na/Ca exchanger

Answer 33

3 Na in | 1 Ca out

Question 34

What does the Na/Ca exchanger rely on

Answer 34

Na gradient

Question 35

Can the Na/Ca exchanger reverse? Where is this seen?

Answer 35

Can switch 3 Na out 1 Ca in Seen during systole in the heart

Question 36

Is the Na/Ca exchanger electrogenic

Answer 36

Yes 3 positive charges in, only 2 out

Question 37

The Na/Ca exchanger does what to the Na gradient

Answer 37

Magnifies it

Question 38

What is the normal Na gradeint

Answer 38

10x

Question 39

What is the effect of magnification of the gradient

Answer 39

Cubing 10^3

Question 40

What gene family is Na/Ca exchanger belonging to

Answer 40

SLC8

Question 41

What is the superfamily that Na/Ca exchanger belongs to

Answer 41

CaCA

Question 42

Model for the Na/Ca exchanger action

Answer 42

``` 3 Na in EC bind Conf change Na released to IC 1 Ca from IC binds Conf change Ca released to EC ```

Question 43

Two transport proteins responsible for maintaining Ca gradient

Answer 43

Na/Ca exchanger | Ca ATPase

Question 44

What type of ATP ase is the Ca ATPase

Answer 44

P type

Question 45

What three Ca ATPases are found in cells

Answer 45

PMCA SERCA SPCA

Question 46

PMCA

Answer 46

Plasma membrane Ca pumps

Question 47

SERCA

Answer 47

Sarcoplasmic reticulum/endoplasmic reticulum Ca pumps

Question 48

SPCA

Answer 48

Golgi Ca pumps

Question 49

What is the functional model for the Ca ATPase

Answer 49

``` Binding Phosphorylation Conf change Release Dephosphorylation Conformatioanl change Repeat ```

Question 50

What can the Ca ATPase also transport

Answer 50

Protons

Question 51

Ca signalling | Stimuli that cause entry

Answer 51

VGCC Receptor operated Ca channels - e.g. in secretory cells and nerve terminals e.g. NMDA Mechanically activated Ca channels Store operated channels

Question 52

Two store pathways for Ca

Answer 52

IP3 receptors | Ryanodine receptors

Question 53

IP3 receptor pathway

Answer 53

PLC converts PI(4,5)P2 to Ip3 and DAG | Ip3 acts on the store channels

Question 54

Ryanodine store pathway

Answer 54

Act. by a low conc of ryanodine Inhib by a high concentration of ryanodine Natural activator is cADP ribose

Question 55

What is the natural activator of ryanodine store pathway

Answer 55

cADP ribose

Question 56

What is the effect of high concnetrations of ryanodine on the store pathway

Answer 56

Inhibition

Question 57

What is the effect of low concentrations of ryanodine on the store pathway

Answer 57

Activation

Question 58

Describe how the Ca stores are able to replenish once depleted

Answer 58

When depleted there is a conformational change in STIM proteins DIMERS form MULTIMERS More confirmational changes cause STIMs to bind to cell membrane Activation of Ca channels Ca taken up into the stores Ca binds to STIM and the process reverses