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Membranes and Receptors > Session 2 - Ion pumps and exchangers > Flashcards

Session 2 - Ion pumps and exchangers Flashcards

0
Q

What is passive diffusion dependant upon?

A
  • Membrane permeability

- Concentration gradients

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1
Q

List some functions which transporter proteins are important for

A
  • Maintain intracellular pH
  • Maintain ionic composition and gradients
  • Regulation of cell volume
  • Regulation of metabolite concentration within cells
  • Extrusion of waste products
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2
Q

What are the two ways in which facillitated diffusion of molecules occurs?

A
  • Molecule binds to transporter channel, conformational change, molecule released on opposite side
  • Channel/transporter is opened in response to a stimulus allowing passage of molecule to other side
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3
Q

What are ligand-gated ion channels?

A

-Channels which open in response to the binding of a ligand from a stimulus (form of facilitated diffusion)

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4
Q

What are voltage-gated ion channels?

A

-Channels which open/close dependant on the potential difference across a membrane

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5
Q

Give an example of a ligand-gated ion channel

A
  • Nicotinic Ach Receptor (allow passage of Na+)

- ATP-sensitive K+ channels

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6
Q

What is a co-transporter?

A

-A transporter/channel which transports more than 1 type of molecule

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7
Q

Why does active transport require energy?

A

-Moves molecules against their concentration gradient

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8
Q

What is the difference between primary and secondary active transport?

A
  • Primary uses ATP directly

- Secondary uses ATP indirectly by using an ion gradient set up using ATP

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9
Q

What are secondary active transporters?

A

-Co-transporter which are dependant upon an ionic gradient

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10
Q

What is a uniport transporter?

A

-Transports one molecule in one direction

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11
Q

What is a symport transporter?

A

-Transports two types of molecule in the same direction

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12
Q

What is an antiport transporter?

A

-Transports two different type of molecules in opposite directions

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13
Q

Give an example of a symport secondary active transporter in the small intestine

A

-Na+-glucose transporter uses Na gradient to transport glucose against its concentration gradient

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14
Q

Give an example of a antiport secondary active transporter used in alkalising cells and explain

A
  • NaH exhanger
  • Na pumped inwards, down its concentration gradient and uses the energy from that to extrude H+ ion which leads to the cell being more allkaline
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15
Q

What ion/ion channel is mainly responsible for setting up the resting membrane potential?

A

-K+ through voltage-insensitive K channels

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16
Q

What pump is essential in maintaining Na and K concentration gradients?

A

-Na+K+ATPase

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17
Q

What type of active transport does NaKATPase use?

A

-Primary

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18
Q

What molecules are involved in one cycle of the NaK pump?

A
  • 1 ATP
  • 3Na out
  • 2K in
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19
Q

What type of transporter is NaK pump? (port-wise)

A

-Antiport

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20
Q

NaKATPase is a P-type ATPase, what does this mean?

A

-ATP hydrolysis phosphorylates aspartate on the pump which results in the production of phosphoenzyme intermediate which drives conformational change of the pump

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21
Q

What is the a-subunit of NaKATPase responsible for?

A

-Contains the binding sites

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22
Q

What is the b-subunit of NaKATPase responsible for?

A

-Contains glycoproteins which directs pump to the cell membrane

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23
Q

What is the consequence of binding ouabain to the NaKATPase?

A

-Inhibition

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24
Q

Why is the NaKATPase essential?

A

-Maintains the Na and K gradients which are necessary for secondary active transport and thus cell functions

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25
Q

List some cell functions/regulations which rely upon secondary active transport

A
  • Regulation of pH
  • Regulation of cell volume
  • Regulation of Ca2+ conc
  • Nutrient uptake eg glucose
  • Absorption of Na+ in epithelia
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26
Q

Name two primary Ca2+ATPases

A
  • Plasma Membrane Ca2+ ATPase (PMCA)

- Sarco/Endo Reticulum Ca2+ ATPase (SERCA)

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27
Q

How do the mitochondria act as a buffer for Ca?

A

-Has a Ca2+ uniporter to allow calcium into the mitochondria when intracellular calcium reaches dangerous levels

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28
Q

What does PMCA transport?

A
  • Ca2+ out

- H+ in

29
Q

What type of port is PMCA?

A

-Antiport

30
Q

When does PMCA become active and how is its affinity/capacity adapted for this?

A
  • To remove the residual Ca in the cell
  • High affinity
  • Low capacity
31
Q

What type of port is SERCA?

A

-Antiport

32
Q

What is the function of SERCA?

A

-To decrease intracellular calcium levels by acting as a store for calcium

33
Q

What does SERCA transport?

A
  • Ca2+ into SR

- H+ into cell

34
Q

What is SERCAs affinity/capacity and how does this reflect its function?

A
  • High affiinity
  • Low capacity
  • Removes residual Ca in order to keep intracellular Ca really low
35
Q

Name a secondary active Ca transporter

A

-NaCa exchange (NCX)

36
Q

How is NCX a secondary transporter?

A

-Uses the Na gradient set up by NaKATPase to pump Ca against its concentration

37
Q

What does NCX transport?

A

-3Na for every 1Ca

38
Q

Why is NCX activity said to be membrane potential-dependent?

A
  • If the membrane is polarised (Na is low and Ca is high) NCX pumps 3Na in, down its concentration gradient, and pumps 1Ca out
  • During depolarisation(Na is high and Ca is low), NCX changes direction and pumps 3Na out and 1Ca in
39
Q

What is the affinity/capacity of NCX and how does this reflect its function?

A
  • Low affinity
  • High capacity
  • NCX works when there is high amounts of the substrate, ie after depolarisation there is high amount of Ca in the cell so expels Ca, or during depolarisation there is high amounts of Na so expels Na
40
Q

What happens to NCX during ischaemia?

A
  • ATP depleted
  • NaKATPase inhibited
  • Na accumulates
  • NCX reverses and pumps Na out the cell and thus brings Ca in
  • Ca is toxic in high concs
41
Q

State the normal extracellular and intracellular levels of Na

A
  • 145mM extracellularly

- 12mM intracellularly

42
Q

State the normal values of K extracellularly and intracellularly

A
  • 4mM extracellularly

- 155mM intracellularly

43
Q

State the normal values of Cl extracellularly and intracellularly

A
  • 123 extracellularly

- 4.2 intracellularly

44
Q

State the values of Ca extracellularly and intracellularly

A
  • 1.5mM extracellularly

- 10-7mM intracellularly

45
Q

Name 2 acid extruders

A
  • NaH exchanger

- Na-dependant H+/Cl-/HCO3- exchanger (NBC)

46
Q

What does the NHE transport?

A
  • 1 Na into the cell

- 1 H+ out of the cell

47
Q

Why does NHE effect osmotic potential but not membrane potential of cells?

A
  • Exchange is on a 1:1 charge basis so memb potential does not change
  • The ions have different osmotic potentials
48
Q

In what way does NHE change intracellular pH?

A

-Increases it

49
Q

Why is NHE known as a secondary active transporter?

A

-Uses the gradient maintained by NaKATPase to drive the expulsion of H+

50
Q

What drug inhibits NHE?

A

-Amiloride

51
Q

What ions does ant NBC transport?

A
  • Na in and H out

- HCO3 in and Cl out

52
Q

Is NBC a primary or secondary active transporter?

A

-Secondary

53
Q

What effect does NBC have in intracellular pH?

A

-Increases it

54
Q

Name a base extruder

A

-Anion echanger

55
Q

What ions does anion exchanger transport?

A
  • HCO3 out

- Cl in

56
Q

What effect does anion exchanger have on intracellular pH?

A

-Decreases it

57
Q

What ultimately controls the activity of acid/base extruders?

A

-The pH in the cell

58
Q

What extruders are activated if a cell becomes acidified?

A

-Acid extruders NHE and NBC

59
Q

What transporters become activated if a cell become alkaline?

A

-Base extruder (AE)

60
Q

How is cell volume regulated?

A

-Through a combination of different transporters extruding/influxing osmotically active ions

61
Q

In which direction do osmotically active ions move during cell swelling?

A

-They are extruded

62
Q

In which direction do osmotically active ions move if there is cell shrinkage?

A

-They are influxed

63
Q

What are the main osmotically active ions?

A
  • Na+
  • K+
  • Cl-
  • HCO3-
64
Q

How does bicarbonate reabsorption occur in the proximal convoluted tubule?

A
  • NaKATPase keeps intracellular Na low
  • NHE exchanges Na in and extrudes H out into the lumen
  • H reacts with bicarbonate to form carbonic acid which dissociates into CO2
  • CO2 diffuses down its conc gradient into cell
  • CO2 combines with H20 and forms carbonic acid
  • Carbonic acid dissociates into HCO3 and H+
  • HCO3 pumped into blood by anion exchanger
65
Q

What drug can be used to block NHE in proximal convoluted tubule?

A

-Amiloride

66
Q

When would amiloride be used? How is it helpful?

A
  • As a diuretic in anti-hypertensive treatment
  • Blocks NHE preventing uptake of Na
  • Stops water reabsorption
  • Decreased blood volume
  • Decreases blood pressure
67
Q

What do you have to be careful of if using amiloride as a anti-hypertensive treatment?

A
  • Bicarbonate reabsoprtion

- Blocking NHE will reduce bicarbonate reabsorption which is necessary for a pH buffer in cells

68
Q

What is the aim of diuretics?

A
  • Reduce uptake of NA and thus decrease water reabsortion

- Blood vol will fall followed by blood pressure

69
Q

Describe a diuretic used to block Na uptake in thick ascending limb

A
  • Loop diuretic

- Blocks NKCC2 channel so Na not reabsorbed

70
Q

Describe a drug used to block Na uptake in distal convoluted tubule

A

-Amiloride blocks Epithelial Na Channel

71
Q

Describe a drug used to treat hypertesion caused by high aldosterone

A
  • Spironolactone is a glucocorticoid receptor blocker
  • Blocking aldosterone receptors will decrease stimulation of Na uptake
  • Aldosterone also upregulates aquaporin channels -> blocking aldosterone will stop upregulation of these channels and decrease water reabsorption

Membranes and Receptors (13 decks)

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