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ESA 2- Membranes and Receptors > ATP-Dependant Ion Pumps and Ion Exchangers > Flashcards

ATP-Dependant Ion Pumps and Ion Exchangers Flashcards

1
Q

What molecules can pass through membranes?

A

Hydrophobic or Small, uncharged, polar molecules

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2
Q

What molecules cannot pass through membranes?

A

Large, uncharged polar molecules

Ions

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3
Q

What is passive diffusion dependent on?

A

Permeability and concentration gradient

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4
Q

What happens to the rate of passive transport with an increasing concentration gradient?

A

It increases linearly

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5
Q

What is the permeability of the membrane for a substance increased by?

A

The incorporation of a specific protein in the bilayer

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6
Q

Give two examples of models for facilitated diffusion

A 
Carrier molecules (ping-pong)
 Protein channels
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7
Q

What does active transport allow?

A

The transport of ions or molecules against an unfavourable concentration and/or electrical gradient

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8
Q

What does active transport require?

A

Energy from the hydrolysis of ATP

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9
Q

What is wether or not energy is required determined by?

A

The free energy change of the transported species

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10
Q

What is the free energy change of the transported species dependant on?

A

The free energy change of the transported species, and by the electrical potential across the membrane bilayer when the transported species is charged

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11
Q

How much of a cells energy is spent on active transport?

A

In some cells, up to 30-50%

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12
Q

What happens when pores are gated?

A

They open and close in response to a stimulus

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13
Q

Give examples of a stimulus that might open a pore?

A

Ligand binding to a receptor site
Change in potential difference across the membrane
ATP binding

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14
Q

Give an example of a voltage-gated ion channel

A

Na channel

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15
Q

Give examples of a ligand-gated ion channels

A

Nicotinic acetylcholine receptor

ATP-sensitive K channel

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16
Q

Can more than one type of ion/molecule be transported on a membrane transporter per reaction cycle?

A

Yes

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17
Q

What are membrane transporters that transport more than one molecule known as?

A

Co-transporters

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18
Q

Give examples of co-transport

A

Na-glucose co-transport system of the small intenstine and kidney
Na/H exchange

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19
Q

What happens in Na/H exchange?

A

Inwards flow of Na down its concentration gradient leads to removal of H, and a rise in cell pH

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20
Q

What is a transported in a uniport?

A

A single molecule in one direction

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21
Q

What is transported in a symport?

A

Two molecules, in the same direction

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22
Q

What is transported in an antiport?

A

Two molecules in opposing directions

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23
Q

Where does Na-glucose co-transport occur?

A

Small intestine and kidney

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24
Q

What happens in Na-glucose co-transport?

A

Entry of Na provides the energy for the entry of glucose against the concentration gradient

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25
What kind of transporter is the Na-glucose transporter?
Symport
26
Where is Na/K-ATPase associated?
Plasma membrane
27
What does Na/K-ATPase use to pump ions?
ATP
28
How much of the BMR is used for the Na/K-ATPase?
25%
29
What kind of ATPase is Na/K-ATPase?
P-type
30
What do P-type ATPases do?
ATP phosphorylates aspartate, producing phosphoenzyme intermediates
31
What is the Na/K-ATPase made up of?
α and ß subunits
32
What does the α-subunit do?
Provides the binding site for K, Na, ATP and ouabain
33
What does the ß subunit do?
Glycoprotein directs pump to the surface
34
What does the binding of ouabain to the α-subunit do?
Inhibits Na/K-ATPase
35
What does the Na/K-ATPase do?
Uses energy from ATP hydrolysis to make 2K into the cell and 3 Na out of the cell
36
What kind of transporter is Na/K-ATPase?
Antiport
37
Why is Na/K-ATPase important?
It forms Na and K gradients
38
What are Na and K gradients necessary for?
Electrical excitability
39
What does Na/K-ATPase drive?
Secondary active transport
40
What processes are driven by active transport secondary to the Na/K-ATPase?
``` Control of pH  Regulation of cell volume  Regulation of Ca concentration  Absorption of Na in epithelia  Nutrient uptake ```
41
What is the resting membrane potential?
-70mV
42
What is responsible for the membrane potential?
Mainly, K+ diffusion through channels down its concentration gradient (there are high intracellular K concentrations)
43
What causes high intracellular K concentrations?
Na pump
44
What controls resting Ca concentration?
Ca-ATPases
45
How do Ca-ATPases work?
They use ATP to pump ions
46
What does plasma membrane Ca-ATPase (PMCA) do?
Expels Ca from the cell in exchange for H
47
What does PMCA require?
ATP
48
What kind of transporter is PMCA?
Antiport
49
What is the affinity of PMCA?
High
50
What is the capacity of PMCA?
Low
51
What does PMCA remove?
Residual Ca
52
What does the sarco(endo)plasmic reticulum Ca-ATPase (SERCA) do?
Accumulates Ca into the SR/ER in exchange for H
53
What does SERCA use?
ATP
54
What kind of transporter is SERCA?
Antiport
55
What is the affinity of SERCA?
High
56
What is the capacity of SERCA?
Low
57
What does SERCA remove?
Residual Ca
58
How is the Na/Ca exchanger (NCX) driven?
Secondary active transport, using the Na concentration gradient set up by Na/K-ATPase
59
What does NCX do?
Expels 1 Ca from the cell in exchange for 3 Na
60
What kind of transporter is NCX?
Antiport
61
What is the affinity of NCX?
Low
62
What is the capacity of NCX?
High
63
What does NCX remove?
Most Ca
64
Why is NCX said to be electrogenic?
Because current flows in the direction of the Na gradient
65
When does NCX expel intracellular Ca?
During cell recovery
66
What is the activity of NCX dependant on?
Membrane potential
67
What happens to NCX when the membrane is depolarised?
It reverses the mode of operation
68
Give an example of where the reversal of the NCX mode of operation is important?
Ca influx during the cardiac action potential
69
How can NCX contribute to ischaemic injury?
ATP is depleted in ischaemia, and the Na pump is therefore inhibited, so Na accumulates in the cell, leading to depolarisation, and so NCX reverse. Na moves out, Ca moves in. High Ca is toxic
70
What are the two acid extruders?
Na/H exchanger (NHE) | Sodium bicarbonate co-transporter (NBC)
71
What does NHE do?
Exchanges extracellular Na for intracellular H
72
Is NHE electrogenic?
No- it is electroneutral
73
Why is NHE electroneutral?
Because there is 1:1 charge exchange
74
What does NHE use to drive it?
The Na concentration gradient set up by Na/K-ATPase
75
What does NHE act to do?
Raise intracellular pH and regulate cell volume
76
What activates NHE?
Growth factors
77
What inhibits NHE?
Amiloride
78
What is NBC also known as?
Na dependent Cl/HCO3 exchanger
79
Essentially, what happens with NBC?
Acid out  | Base in
80
What does NBC use?
The Na concentration gradient set up by Na/K-ATPase
81
What does NBC act to do?
Raise intracellular pH | Regulate cell volume
82
What is the base extruder?
Anion exchanger (AE)
83
What does the AE do?
Exchanges Cl for HCO3-
84
What does the AE serve to do?
Acidify cell  | Involved in cell volume regulation
85
What happens to pH in the cell?
It is held at the set point. Any drift away from this pH is corrected by the increased activity of exchangers
86
What happens as the cell becomes more acidic?
There is more substrate for NHE, and so more acid is removed from the cell, so the pH is restored towards alkaline
87
What happens as NHS extrudes too many H ions?
The pH goes where it needs to be, and so the activity of the anion exchanger cuts in
88
How does ion transport regulate cell volume?
Osmotically active ions or organic osmolytes are transported either into or out of cells, and water follows, causing cell swelling and shrinking
89
Give 3 examples of osmotically active ions
Na K Cl
90
What are organic osmolytes?
Amino acids
91
What is the standard method for cell volume regulation?
There is no standard method- different cell types use particular combinations of transporters to achieve the regulation they need
92
What happens if the cell is swelling?
Ions are extruded, e.g. through K and Cl channels, and so water is lost
93
What happens if the cell is shrinking?
There is an influx of ions, e.g. through Na and Ca channels, and so water is gained
94
How is bicarbonate reabsorbed by the proximal kidney tubule?
Na/K pump drives other channels, in this case keeping intracellular Na concentration low, so NHE can pump H ions into the proximal tubule lumen. H then goes into the lumen to ‘pick up’ bicarbonate and bring it back into the cell
95
How much bicarbonate does the kidney reabsorb under normal circumstances?
All of it
96
What is the main reason to retain base?
For pH buffers
97
What is the goal of renal anti-hypertensive therapy?
To reduce the reuptake of Na and other molecules, so less water is absorbed by osmosis, and so blood volume and therefore blood pressure falls
98
What are aquaporin allow?
Water to more readily cross the membrane
99
What is aquaporins inclusion in the membrane stimulated by?
Anti-diuretic hormone (ADH)
100
What mechanisms to allow Na reuptake from the filtrate to the blood are there in the thick ascending limb?
NKCC2  | Na-K-ATPase
101
What does NKCC2 do?
Moves Na, K and 2Cl into the endothelium of the nephron
102
How does NKCC2 move Na into the blood?
Using the Na gradient to drive Na
103
How is Na passed from endothelium into the blood?
Na-K-ATPase
104
What is required due to the action of NKCC2?
The kidney needs to deal with the K and Cl bought in if it wants to maintain the same potential
105
What mechanisms does the thick ascending limb have to deal with K and Cl?
KClCT  | ROMK
106
What does KClCT do?
K-Cl cotransport that salvages both ions back into the blood
107
What does ROMK do?
Allows efflux of K back into filtrate
108
What blocks the action of NKCC2?
Loop diuretics
109
What is the effect of loop diuretics?
They bind to NKCC2 transporters, inhibiting them and therefore more Na is lost in the filtrate. Water follows, thus reducing blood volume, thus blood pressure
110
What is the purpose of the distal convoluted tubule?
To allow ions to equilibrate
111
What mechanisms are present in the distal convoluted tubule?
``` NCCT ENaC TRPM6 CIC-K6 KCICT NCX Na pump ```
112
What does NCCT do?
Cotransport of Na and Cl
113
What inhibits NCCT?
Thiazides
114
What does ENaC do?
Allow Na into the endothelium of nephron
115
Is ENaC voltage sensitive?
No
116
What inhibits ENaC?
Amiloride
117
What does TRPM6 do?
Allows Ca and Mg into the endothelium of the nephron, and thus allowing retention of Ca
118
What does CIC-K6 do?
Brings Cl into the blood from the endothelium
119
What does NCX do?
Brings 3 Na into endothelium for 1 Ca into blood
120
What mechanisms does the cortical collecting tube have?
``` Aquaporin ROMK ENaC CLC Na pump ```
121
What does aquaporin do?
Allows water into blood
122
Why is it important that water is taken up in the kidney?
So it allows water to follow Na, maintaining blood pressure
123
What stimulates aquaporin?
Anti-diuertic hormone
124
What does ROMK do?
Allows K efflux into blood
125
What does ClC do?
Allows Cl into the blood
126
What does aldosterone do?
Upregulates ENaC, ROMK and the Na pump, leading to increase Na retention, and therefore increased water retention
127
What is found in some cases of hypertension?
That there is an increased production of aldosterone and therefore over retention of Na through the epithelial sodium channel
128
How can aldosterone stimulated hypertension be treated?
Using spironolactone
129
What is spironolactone?
A mineralocorticoid receptor antagonist
130
What does spironolactone do?
Binds to aldosterone receptors, stopping the overexpression of these proteins

ESA 2- Membranes and Receptors (13 decks)

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