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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
Q

What kind of transporter is the Na-glucose transporter?

A

Symport

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26
Q

Where is Na/K-ATPase associated?

A

Plasma membrane

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27
Q

What does Na/K-ATPase use to pump ions?

A

ATP

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28
Q

How much of the BMR is used for the Na/K-ATPase?

A

25%

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29
Q

What kind of ATPase is Na/K-ATPase?

A

P-type

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30
Q

What do P-type ATPases do?

A

ATP phosphorylates aspartate, producing phosphoenzyme intermediates

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31
Q

What is the Na/K-ATPase made up of?

A

α and ß subunits

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32
Q

What does the α-subunit do?

A

Provides the binding site for K, Na, ATP and ouabain

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33
Q

What does the ß subunit do?

A

Glycoprotein directs pump to the surface

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34
Q

What does the binding of ouabain to the α-subunit do?

A

Inhibits Na/K-ATPase

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35
Q

What does the Na/K-ATPase do?

A

Uses energy from ATP hydrolysis to make 2K into the cell and 3 Na out of the cell

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36
Q

What kind of transporter is Na/K-ATPase?

A

Antiport

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37
Q

Why is Na/K-ATPase important?

A

It forms Na and K gradients

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38
Q

What are Na and K gradients necessary for?

A

Electrical excitability

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39
Q

What does Na/K-ATPase drive?

A

Secondary active transport

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40
Q

What processes are driven by active transport secondary to the Na/K-ATPase?

A 
Control of pH
 Regulation of cell volume
 Regulation of Ca concentration
 Absorption of Na in epithelia
 Nutrient uptake
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41
Q

What is the resting membrane potential?

A

-70mV

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42
Q

What is responsible for the membrane potential?

A

Mainly, K+ diffusion through channels down its concentration gradient (there are high intracellular K concentrations)

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43
Q

What causes high intracellular K concentrations?

A

Na pump

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44
Q

What controls resting Ca concentration?

A

Ca-ATPases

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45
Q

How do Ca-ATPases work?

A

They use ATP to pump ions

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46
Q

What does plasma membrane Ca-ATPase (PMCA) do?

A

Expels Ca from the cell in exchange for H

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47
Q

What does PMCA require?

A

ATP

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48
Q

What kind of transporter is PMCA?

A

Antiport

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49
Q

What is the affinity of PMCA?

A

High

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50
Q

What is the capacity of PMCA?

A

Low

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51
Q

What does PMCA remove?

A

Residual Ca

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52
Q

What does the sarco(endo)plasmic reticulum Ca-ATPase (SERCA) do?

A

Accumulates Ca into the SR/ER in exchange for H

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53
Q

What does SERCA use?

A

ATP

54
Q

What kind of transporter is SERCA?

A

Antiport

55
Q

What is the affinity of SERCA?

A

High

56
Q

What is the capacity of SERCA?

A

Low

57
Q

What does SERCA remove?

A

Residual Ca

58
Q

How is the Na/Ca exchanger (NCX) driven?

A

Secondary active transport, using the Na concentration gradient set up by Na/K-ATPase

59
Q

What does NCX do?

A

Expels 1 Ca from the cell in exchange for 3 Na

60
Q

What kind of transporter is NCX?

A

Antiport

61
Q

What is the affinity of NCX?

A

Low

62
Q

What is the capacity of NCX?

A

High

63
Q

What does NCX remove?

A

Most Ca

64
Q

Why is NCX said to be electrogenic?

A

Because current flows in the direction of the Na gradient

65
Q

When does NCX expel intracellular Ca?

A

During cell recovery

66
Q

What is the activity of NCX dependant on?

A

Membrane potential

67
Q

What happens to NCX when the membrane is depolarised?

A

It reverses the mode of operation

68
Q

Give an example of where the reversal of the NCX mode of operation is important?

A

Ca influx during the cardiac action potential

69
Q

How can NCX contribute to ischaemic injury?

A

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
Q

What are the two acid extruders?

A

Na/H exchanger (NHE)

Sodium bicarbonate co-transporter (NBC)

71
Q

What does NHE do?

A

Exchanges extracellular Na for intracellular H

72
Q

Is NHE electrogenic?

A

No- it is electroneutral

73
Q

Why is NHE electroneutral?

A

Because there is 1:1 charge exchange

74
Q

What does NHE use to drive it?

A

The Na concentration gradient set up by Na/K-ATPase

75
Q

What does NHE act to do?

A

Raise intracellular pH and regulate cell volume

76
Q

What activates NHE?

A

Growth factors

77
Q

What inhibits NHE?

A

Amiloride

78
Q

What is NBC also known as?

A

Na dependent Cl/HCO3 exchanger

79
Q

Essentially, what happens with NBC?

A

Acid out

Base in

80
Q

What does NBC use?

A

The Na concentration gradient set up by Na/K-ATPase

81
Q

What does NBC act to do?

A

Raise intracellular pH

Regulate cell volume

82
Q

What is the base extruder?

A

Anion exchanger (AE)

83
Q

What does the AE do?

A

Exchanges Cl for HCO3-

84
Q

What does the AE serve to do?

A

Acidify cell

Involved in cell volume regulation

85
Q

What happens to pH in the cell?

A

It is held at the set point. Any drift away from this pH is corrected by the increased activity of exchangers

86
Q

What happens as the cell becomes more acidic?

A

There is more substrate for NHE, and so more acid is removed from the cell, so the pH is restored towards alkaline

87
Q

What happens as NHS extrudes too many H ions?

A

The pH goes where it needs to be, and so the activity of the anion exchanger cuts in

88
Q

How does ion transport regulate cell volume?

A

Osmotically active ions or organic osmolytes are transported either into or out of cells, and water follows, causing cell swelling and shrinking

89
Q

Give 3 examples of osmotically active ions

A

Na
K
Cl

90
Q

What are organic osmolytes?

A

Amino acids

91
Q

What is the standard method for cell volume regulation?

A

There is no standard method- different cell types use particular combinations of transporters to achieve the regulation they need

92
Q

What happens if the cell is swelling?

A

Ions are extruded, e.g. through K and Cl channels, and so water is lost

93
Q

What happens if the cell is shrinking?

A

There is an influx of ions, e.g. through Na and Ca channels, and so water is gained

94
Q

How is bicarbonate reabsorbed by the proximal kidney tubule?

A

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
Q

How much bicarbonate does the kidney reabsorb under normal circumstances?

A

All of it

96
Q

What is the main reason to retain base?

A

For pH buffers

97
Q

What is the goal of renal anti-hypertensive therapy?

A

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
Q

What are aquaporin allow?

A

Water to more readily cross the membrane

99
Q

What is aquaporins inclusion in the membrane stimulated by?

A

Anti-diuretic hormone (ADH)

100
Q

What mechanisms to allow Na reuptake from the filtrate to the blood are there in the thick ascending limb?

A

NKCC2

Na-K-ATPase

101
Q

What does NKCC2 do?

A

Moves Na, K and 2Cl into the endothelium of the nephron

102
Q

How does NKCC2 move Na into the blood?

A

Using the Na gradient to drive Na

103
Q

How is Na passed from endothelium into the blood?

A

Na-K-ATPase

104
Q

What is required due to the action of NKCC2?

A

The kidney needs to deal with the K and Cl bought in if it wants to maintain the same potential

105
Q

What mechanisms does the thick ascending limb have to deal with K and Cl?

A

KClCT

ROMK

106
Q

What does KClCT do?

A

K-Cl cotransport that salvages both ions back into the blood

107
Q

What does ROMK do?

A

Allows efflux of K back into filtrate

108
Q

What blocks the action of NKCC2?

A

Loop diuretics

109
Q

What is the effect of loop diuretics?

A

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
Q

What is the purpose of the distal convoluted tubule?

A

To allow ions to equilibrate

111
Q

What mechanisms are present in the distal convoluted tubule?

A 
NCCT
 ENaC
 TRPM6
 CIC-K6
 KCICT
 NCX
 Na pump
112
Q

What does NCCT do?

A

Cotransport of Na and Cl

113
Q

What inhibits NCCT?

A

Thiazides

114
Q

What does ENaC do?

A

Allow Na into the endothelium of nephron

115
Q

Is ENaC voltage sensitive?

A

No

116
Q

What inhibits ENaC?

A

Amiloride

117
Q

What does TRPM6 do?

A

Allows Ca and Mg into the endothelium of the nephron, and thus allowing retention of Ca

118
Q

What does CIC-K6 do?

A

Brings Cl into the blood from the endothelium

119
Q

What does NCX do?

A

Brings 3 Na into endothelium for 1 Ca into blood

120
Q

What mechanisms does the cortical collecting tube have?

A 
Aquaporin
 ROMK
 ENaC
 CLC
 Na pump
121
Q

What does aquaporin do?

A

Allows water into blood

122
Q

Why is it important that water is taken up in the kidney?

A

So it allows water to follow Na, maintaining blood pressure

123
Q

What stimulates aquaporin?

A

Anti-diuertic hormone

124
Q

What does ROMK do?

A

Allows K efflux into blood

125
Q

What does ClC do?

A

Allows Cl into the blood

126
Q

What does aldosterone do?

A

Upregulates ENaC, ROMK and the Na pump, leading to increase Na retention, and therefore increased water retention

127
Q

What is found in some cases of hypertension?

A

That there is an increased production of aldosterone and therefore over retention of Na through the epithelial sodium channel

128
Q

How can aldosterone stimulated hypertension be treated?

A

Using spironolactone

129
Q

What is spironolactone?

A

A mineralocorticoid receptor antagonist

130
Q

What does spironolactone do?

A

Binds to aldosterone receptors, stopping the overexpression of these proteins

ESA 2- Membranes and Receptors (13 decks)

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