M&R Session 2 Flashcards
What are the six roles of transport processes across cell membranes?
Maintenance of ionic composition
Maintenance of intracellular pH
Regulation of cell volume
Regulation of concentration of metabolic fuels and building blocks
Extrusion of waste products
Generation of ion gradients necessary for electrical excitability
What does the rate of passive transport increase linearly with?
Increasing concentration gradient
Name the four models of membrane transport proteins.
Ping-pong transport
Facilitated diffusion via ion channels
Ligand-gated ion channels
Voltage-gated ion channels
How does ping-pong transport work?
Conformational change allows binding of substance and its release on the other side
How does facilitated diffusion via ion channels function?
Pores which open and close in the plasma membrane allow selected ions to pass through
Describe the mechanism of ligand-gated ion channel function.
Ligand binds to receptor –> conformational change –> allows passage of molecule
How do voltage-gated ion channels function?
Membrane depolarisation moves sensor within the channel allowing passage of ions through
Are membrane transport protein mediated processes saturable?
Yes
What determines whether the transport process carried out by a transport protein is active or passive?
Concentration ratio
Membrane potential
What is linearly related to the natural log of the concentration gradient and the potential gradient?
Transport
Where is the energy for active transport derived?
Directly or indirectly from ATP hydrolysis
How much energy is released by the hydrolysis of one molecule of ATP?
-31 kJ per mole
Describe the direction of concentration gradients of sodium, potassium, chloride and calcium ions across the cell membrane.
Sodium in
Chloride in
Potassium out
Calcium in
What is a primary transporter?
A transporter directly involved in the hydrolysis of ATP
What is a cotransporter?
A transport protein which transports more than one type of ion/molecule per reaction cycle
Define uniport, symport and antiport.
Uniport = one ion/molecule transported Symport = 2 on same side Antiport = one on each side
Which is the most important antiporter?
The sodium ion pump
What is the ionic movement of each cycle performed by the sodium pump?
3 sodium in
2 potassium out
What proportion of the BMR is used for the sodium pump?
25%
Why is the sodium pump called a P-type ATPase?
ATP phosphorylates aspartate which produces a phosphoenzyme intermediate so that the phosphate can be lost again freely within the cell
What is the function of the beta subunit of the sodium pump?
Directs it to cell surface
What is the function of the alpha subunit of the sodium pump?
Provides binding sites for: potassium sodium ATP ouabain
What is ouabain?
A cardiac glycoside
Is the sodium pump electrogenic?
Yes
How does the sodium pump facilitate generation of the membrane potential?
Creates high intracellular potassium concentration
Describe the calcium-magnesium-ATPase cotransporter.
Primary active transporter
High affinity
Low capacity
Describe the sodium-calcium exchanger.
Secondary transporter
Low affinity
High capacity
Which cotransporter contributes most to calcium extrusion in high calcium conditions?
Sodium-calcium exchanger
Describe the sodium-hydrogen exchanger.
Secondary active transporter
Antiport
Describe the sodium-glucose cotransporter.
Secondary active transporter
Found in small intestine and kidney
How are cystic fibrosis and diarrhoea linked?
Same transport mechanism in a different cell gives a different effect:
CF - no efflux of chloride –> no water in lumen –> thick mucus
Diarrhoea - protein kinase A activated –> chloride efflux –> water follows
What is the function of sodium-potassium-ATPase?
Electrical excitability
Drives secondary active transport for:
pH control, cell volume and calcium concentration regulation, absorption of sodium and nutrient uptake
Describe the function of PMCA.
Expels calcium
High affinity
Low capacity
Describe the function of the anion exchanger.
Acidifies cell
Hydrogen carbonate out
Chloride in
Describe the function of SERCA.
Accumulates calcium into the SR/ER
High affinity
Low capacity
Describe the ionic movements facilitated by the sodium-calcium exchanger.
Exchanges 3 sodium ions for 1 calcium ion
How does current flow in the sodium-calcium exchanger?
In the direction of the sodium gradient
What does the activity of the NCX depend on?
Membrane potential
When the cell is depolarised, what happens to the mode of operation of the NCX?
It reverses - sodium out and calcium in
How does ischaemia affect the function of the NCX?
Lack of oxygen = ATP depleted –> sodium pump inhibited –> sodium in and cell depolarises –> NCX reverses –> calcium necrosis
Describe the function of the sodium-hydrogen exchanger.
Exchanges extracellular sodium for intracellular hydrogen 1:1
Regulates pH
Regulates cell volume
What acts on the NHE to affect its function?
Activated by growth factors
Inhibited by Amiloride
Why is calcium toxic to cells?
Reacts with key buffer - phosphate
Causes ‘ossification’ of cells
What role do mitochondria have in cellular calcium regulation?
Act as a buffer when levels are dangerously high
Allow facilitated transport via uniports at high concentrations
Which transporters act to alkalinise cells?
NHE
NBC (sodium bicarbonate cotransporter)
Sodium dependent chloride-hydrogen carbonate exchanger
Which transporters are base extruders?
Chloride-hydrogen carbonate exchanger
Anion exchanger
How is a drift away from the set pH of a cell corrected?
Transporters can move the set point
How is cell volume regulated?
Transport of osmotic ally active ions which are followed by water
What is the universal method for cell volume regulation?
There isn’t one - hah!
Different cell types use particular combinations of transporters to achieve the regulation they need
Give the three methods of resisting cell swelling.
Efflux of potassium and chloride
Efflux of amino acids
Influx of hydrogen carbonate and hydrogen ions to form carbonic acid - carbon dioxide and water efflux
Describe the three methods of resisting cell shrinking.
Influx of sodium, potassium, chloride and organic osmolytes
Efflux of hydrogen carbonate and hydrogen from dissociation of carbonic acid
Conductive influx of sodium and calcium
How does the process of resisting cell swelling prevent depolarisation?
It is electroneutral
Describe the reabsorption of filtered bicarbonate.
Normally all reabsorbed in proximal tubule
Needed to retain base for pH buffers
Carbonic anhydride acts in PCT lumen to dissociate bicarbonate for easy diffusion
How does Amiloride act?
Blocks sodium uptake in PCT and DCT
Disrupts bicarbonate transporters
What is hyperaldosterium?
High aldosterone –> excess sodium retention –> high blood pressure
In what order would you try diuretics available for treatment?
Loop diuretics
Thiazide
Spirondactone
What is Spirondactone?
Glucocorticoid receptor antagonist
Which pumps are present in the thick ascending limb?
KClT
ClC-Kb
Sodium pump
Which pumps are present in the distal convoluted tubule?
ClC-Kbps
KClCT
NCX
Sodium pump
Which pumps are found in the cortical collecting duct?
ROMK
Sodium pump
ClC
How does diuretic hormone work?
It acts on the cortical collecting duct to increase aquaporin expression
