L4 - Cell Homeostasis Flashcards Preview

BMS242 Core Phys Pharm > L4 - Cell Homeostasis > Flashcards

Flashcards in L4 - Cell Homeostasis Deck (58)
Loading flashcards...
1

Normal Na IC

10-15 mM

2

Normal Na EC

145-150 mM

3

Why must Na levels be carefully controlled

To drive other secondary active processes inside of the cell

4

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

NHE

5

What process is NHE involved in

Acid extrusion

6

What is the function of the thick ascending limb

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.

7

What is the transepithelial osmotic gradient responsible for

Counter current multipllication

8

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

NaCl reabsorption would be inhibited
Transepithelial osmotic gradient is dissipated

9

Ena

+60 mV

10

Ek

-70/80 mV

11

Vm resting

-70 mV

12

In all cells there is a ____________________________ for Na

Chemical and electrical gradient

13

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

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

14

Sum up the Na/K ATPase

3 NA OUT
2 K IN
USING ATP HYDROLYSIS

15

Model of action of the Na/K ATPase

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

16

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

It is a saturable function of Na i and K o

17

What does a saturable function mean

It will plateau and saturate when working at its max rate

18

What also does the Na/K ATPase rely on

ATP

19

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

Saturable function of [ATP]

20

What type of drug inhibits the Na/K ATPase

Cardiac glycosides

21

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

Ouabaine
Digoxin

22

What does the Na/K ATPase maintain

High Na i
Low Na o

23

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

MINOR and MAJOR

24

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

It is electrogenic - net loss of + from the cell

25

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

Sets up a high K IC and low K EC

Leak current is the driving force for K out of the cell
Vm --> Ek

26

Normal Ca IC

1 mM

27

1 mM to nM

1x 10^6

28

Normal Ca EC

100 nM

29

Roles of Ca inside of cells

Second messenger
Fusion of vesicles to the membrane
Contraction of muscles

30

What is the difference between Ca IC and Ca EC

1000 times difference

31

This huge Ca gradient means

Favours Ca influx

32

E CA

+120 mV

33

Descibe the Na/Ca exchanger

3 Na in
1 Ca out

34

What does the Na/Ca exchanger rely on

Na gradient

35

Can the Na/Ca exchanger reverse?

Where is this seen?

Can switch 3 Na out 1 Ca in

Seen during systole in the heart

36

Is the Na/Ca exchanger electrogenic

Yes

3 positive charges in, only 2 out

37

The Na/Ca exchanger does what to the Na gradient

Magnifies it

38

What is the normal Na gradeint

10x

39

What is the effect of magnification of the gradient

Cubing 10^3

40

What gene family is Na/Ca exchanger belonging to

SLC8

41

What is the superfamily that Na/Ca exchanger belongs to

CaCA

42

Model for the Na/Ca exchanger action

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

43

Two transport proteins responsible for maintaining Ca gradient

Na/Ca exchanger
Ca ATPase

44

What type of ATP ase is the Ca ATPase

P type

45

What three Ca ATPases are found in cells

PMCA
SERCA
SPCA

46

PMCA

Plasma membrane Ca pumps

47

SERCA

Sarcoplasmic reticulum/endoplasmic reticulum Ca pumps

48

SPCA

Golgi Ca pumps

49

What is the functional model for the Ca ATPase

Binding
Phosphorylation
Conf change
Release
Dephosphorylation
Conformatioanl change
Repeat

50

What can the Ca ATPase also transport

Protons

51

Ca signalling
Stimuli that cause entry

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

52

Two store pathways for Ca

IP3 receptors
Ryanodine receptors

53

IP3 receptor pathway

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

54

Ryanodine store pathway

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

55

What is the natural activator of ryanodine store pathway

cADP ribose

56

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

Inhibition

57

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

Activation

58

Describe how the Ca stores are able to replenish once depleted

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