L4 - Cell Homeostasis Flashcards

1
Q

Normal Na IC

A

10-15 mM

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2
Q

Normal Na EC

A

145-150 mM

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3
Q

Why must Na levels be carefully controlled

A

To drive other secondary active processes inside of the cell

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4
Q

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

A

NHE

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5
Q

What process is NHE involved in

A

Acid extrusion

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6
Q

What is the function of the thick ascending limb

A

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.

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7
Q

What is the transepithelial osmotic gradient responsible for

A

Counter current multipllication

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8
Q

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

A

NaCl reabsorption would be inhibited

Transepithelial osmotic gradient is dissipated

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9
Q

Ena

A

+60 mV

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10
Q

Ek

A

-70/80 mV

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11
Q

Vm resting

A

-70 mV

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12
Q

In all cells there is a ____________________________ for Na

A

Chemical and electrical gradient

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13
Q

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

A

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

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14
Q

Sum up the Na/K ATPase

A

3 NA OUT
2 K IN
USING ATP HYDROLYSIS

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15
Q

Model of action of the Na/K ATPase

A
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
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16
Q

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

A

It is a saturable function of Na i and K o

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17
Q

What does a saturable function mean

A

It will plateau and saturate when working at its max rate

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18
Q

What also does the Na/K ATPase rely on

A

ATP

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19
Q

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

A

Saturable function of [ATP]

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20
Q

What type of drug inhibits the Na/K ATPase

A

Cardiac glycosides

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21
Q

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

A

Ouabaine

Digoxin

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22
Q

What does the Na/K ATPase maintain

A

High Na i

Low Na o

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23
Q

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

A

MINOR and MAJOR

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24
Q

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

A

It is electrogenic - net loss of + from the cell

25
Q

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

A

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
Q

Normal Ca IC

A

1 mM

27
Q

1 mM to nM

A

1x 10^6

28
Q

Normal Ca EC

A

100 nM

29
Q

Roles of Ca inside of cells

A

Second messenger
Fusion of vesicles to the membrane
Contraction of muscles

30
Q

What is the difference between Ca IC and Ca EC

A

1000 times difference

31
Q

This huge Ca gradient means

A

Favours Ca influx

32
Q

E CA

A

+120 mV

33
Q

Descibe the Na/Ca exchanger

A

3 Na in

1 Ca out

34
Q

What does the Na/Ca exchanger rely on

A

Na gradient

35
Q

Can the Na/Ca exchanger reverse?

Where is this seen?

A

Can switch 3 Na out 1 Ca in

Seen during systole in the heart

36
Q

Is the Na/Ca exchanger electrogenic

A

Yes

3 positive charges in, only 2 out

37
Q

The Na/Ca exchanger does what to the Na gradient

A

Magnifies it

38
Q

What is the normal Na gradeint

A

10x

39
Q

What is the effect of magnification of the gradient

A

Cubing 10^3

40
Q

What gene family is Na/Ca exchanger belonging to

A

SLC8

41
Q

What is the superfamily that Na/Ca exchanger belongs to

A

CaCA

42
Q

Model for the Na/Ca exchanger action

A
3 Na in EC bind
Conf change 
Na released to IC 
1 Ca from IC binds 
Conf change 
Ca released to EC
43
Q

Two transport proteins responsible for maintaining Ca gradient

A

Na/Ca exchanger

Ca ATPase

44
Q

What type of ATP ase is the Ca ATPase

A

P type

45
Q

What three Ca ATPases are found in cells

A

PMCA
SERCA
SPCA

46
Q

PMCA

A

Plasma membrane Ca pumps

47
Q

SERCA

A

Sarcoplasmic reticulum/endoplasmic reticulum Ca pumps

48
Q

SPCA

A

Golgi Ca pumps

49
Q

What is the functional model for the Ca ATPase

A
Binding 
Phosphorylation 
Conf change 
Release
Dephosphorylation 
Conformatioanl change 
Repeat
50
Q

What can the Ca ATPase also transport

A

Protons

51
Q

Ca signalling

Stimuli that cause entry

A

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

52
Q

Two store pathways for Ca

A

IP3 receptors

Ryanodine receptors

53
Q

IP3 receptor pathway

A

PLC converts PI(4,5)P2 to Ip3 and DAG

Ip3 acts on the store channels

54
Q

Ryanodine store pathway

A

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

55
Q

What is the natural activator of ryanodine store pathway

A

cADP ribose

56
Q

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

A

Inhibition

57
Q

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

A

Activation

58
Q

Describe how the Ca stores are able to replenish once depleted

A

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