Flashcards in L4 - Cell Homeostasis Deck (58)
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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
