ATP-Dependant Ion Pumps and Ion Exchangers Flashcards
What molecules can pass through membranes?
Hydrophobic or Small, uncharged, polar molecules
What molecules cannot pass through membranes?
Large, uncharged polar molecules
Ions
What is passive diffusion dependent on?
Permeability and concentration gradient
What happens to the rate of passive transport with an increasing concentration gradient?
It increases linearly
What is the permeability of the membrane for a substance increased by?
The incorporation of a specific protein in the bilayer
Give two examples of models for facilitated diffusion
Carrier molecules (ping-pong) Protein channels
What does active transport allow?
The transport of ions or molecules against an unfavourable concentration and/or electrical gradient
What does active transport require?
Energy from the hydrolysis of ATP
What is wether or not energy is required determined by?
The free energy change of the transported species
What is the free energy change of the transported species dependant on?
The free energy change of the transported species, and by the electrical potential across the membrane bilayer when the transported species is charged
How much of a cells energy is spent on active transport?
In some cells, up to 30-50%
What happens when pores are gated?
They open and close in response to a stimulus
Give examples of a stimulus that might open a pore?
Ligand binding to a receptor site
Change in potential difference across the membrane
ATP binding
Give an example of a voltage-gated ion channel
Na channel
Give examples of a ligand-gated ion channels
Nicotinic acetylcholine receptor
ATP-sensitive K channel
Can more than one type of ion/molecule be transported on a membrane transporter per reaction cycle?
Yes
What are membrane transporters that transport more than one molecule known as?
Co-transporters
Give examples of co-transport
Na-glucose co-transport system of the small intenstine and kidney
Na/H exchange
What happens in Na/H exchange?
Inwards flow of Na down its concentration gradient leads to removal of H, and a rise in cell pH
What is a transported in a uniport?
A single molecule in one direction
What is transported in a symport?
Two molecules, in the same direction
What is transported in an antiport?
Two molecules in opposing directions
Where does Na-glucose co-transport occur?
Small intestine and kidney
What happens in Na-glucose co-transport?
Entry of Na provides the energy for the entry of glucose against the concentration gradient
What kind of transporter is the Na-glucose transporter?
Symport
Where is Na/K-ATPase associated?
Plasma membrane
What does Na/K-ATPase use to pump ions?
ATP
How much of the BMR is used for the Na/K-ATPase?
25%
What kind of ATPase is Na/K-ATPase?
P-type
What do P-type ATPases do?
ATP phosphorylates aspartate, producing phosphoenzyme intermediates
What is the Na/K-ATPase made up of?
α and ß subunits
What does the α-subunit do?
Provides the binding site for K, Na, ATP and ouabain
What does the ß subunit do?
Glycoprotein directs pump to the surface
What does the binding of ouabain to the α-subunit do?
Inhibits Na/K-ATPase
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
What kind of transporter is Na/K-ATPase?
Antiport
Why is Na/K-ATPase important?
It forms Na and K gradients
What are Na and K gradients necessary for?
Electrical excitability
What does Na/K-ATPase drive?
Secondary active transport
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
What is the resting membrane potential?
-70mV
What is responsible for the membrane potential?
Mainly, K+ diffusion through channels down its concentration gradient (there are high intracellular K concentrations)
What causes high intracellular K concentrations?
Na pump
What controls resting Ca concentration?
Ca-ATPases
How do Ca-ATPases work?
They use ATP to pump ions
What does plasma membrane Ca-ATPase (PMCA) do?
Expels Ca from the cell in exchange for H
What does PMCA require?
ATP
What kind of transporter is PMCA?
Antiport
What is the affinity of PMCA?
High
What is the capacity of PMCA?
Low
What does PMCA remove?
Residual Ca
What does the sarco(endo)plasmic reticulum Ca-ATPase (SERCA) do?
Accumulates Ca into the SR/ER in exchange for H
What does SERCA use?
ATP
What kind of transporter is SERCA?
Antiport
What is the affinity of SERCA?
High
What is the capacity of SERCA?
Low
What does SERCA remove?
Residual Ca
How is the Na/Ca exchanger (NCX) driven?
Secondary active transport, using the Na concentration gradient set up by Na/K-ATPase
What does NCX do?
Expels 1 Ca from the cell in exchange for 3 Na
What kind of transporter is NCX?
Antiport
What is the affinity of NCX?
Low
What is the capacity of NCX?
High
What does NCX remove?
Most Ca
Why is NCX said to be electrogenic?
Because current flows in the direction of the Na gradient
When does NCX expel intracellular Ca?
During cell recovery
What is the activity of NCX dependant on?
Membrane potential
What happens to NCX when the membrane is depolarised?
It reverses the mode of operation
Give an example of where the reversal of the NCX mode of operation is important?
Ca influx during the cardiac action potential
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
What are the two acid extruders?
Na/H exchanger (NHE)
Sodium bicarbonate co-transporter (NBC)
What does NHE do?
Exchanges extracellular Na for intracellular H
Is NHE electrogenic?
No- it is electroneutral
Why is NHE electroneutral?
Because there is 1:1 charge exchange
What does NHE use to drive it?
The Na concentration gradient set up by Na/K-ATPase
What does NHE act to do?
Raise intracellular pH and regulate cell volume
What activates NHE?
Growth factors
What inhibits NHE?
Amiloride
What is NBC also known as?
Na dependent Cl/HCO3 exchanger
Essentially, what happens with NBC?
Acid out
Base in
What does NBC use?
The Na concentration gradient set up by Na/K-ATPase
What does NBC act to do?
Raise intracellular pH
Regulate cell volume
What is the base extruder?
Anion exchanger (AE)
What does the AE do?
Exchanges Cl for HCO3-
What does the AE serve to do?
Acidify cell
Involved in cell volume regulation
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
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
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
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
Give 3 examples of osmotically active ions
Na
K
Cl
What are organic osmolytes?
Amino acids
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
What happens if the cell is swelling?
Ions are extruded, e.g. through K and Cl channels, and so water is lost
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
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
How much bicarbonate does the kidney reabsorb under normal circumstances?
All of it
What is the main reason to retain base?
For pH buffers
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
What are aquaporin allow?
Water to more readily cross the membrane
What is aquaporins inclusion in the membrane stimulated by?
Anti-diuretic hormone (ADH)
What mechanisms to allow Na reuptake from the filtrate to the blood are there in the thick ascending limb?
NKCC2
Na-K-ATPase
What does NKCC2 do?
Moves Na, K and 2Cl into the endothelium of the nephron
How does NKCC2 move Na into the blood?
Using the Na gradient to drive Na
How is Na passed from endothelium into the blood?
Na-K-ATPase
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
What mechanisms does the thick ascending limb have to deal with K and Cl?
KClCT
ROMK
What does KClCT do?
K-Cl cotransport that salvages both ions back into the blood
What does ROMK do?
Allows efflux of K back into filtrate
What blocks the action of NKCC2?
Loop diuretics
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
What is the purpose of the distal convoluted tubule?
To allow ions to equilibrate
What mechanisms are present in the distal convoluted tubule?
NCCT ENaC TRPM6 CIC-K6 KCICT NCX Na pump
What does NCCT do?
Cotransport of Na and Cl
What inhibits NCCT?
Thiazides
What does ENaC do?
Allow Na into the endothelium of nephron
Is ENaC voltage sensitive?
No
What inhibits ENaC?
Amiloride
What does TRPM6 do?
Allows Ca and Mg into the endothelium of the nephron, and thus allowing retention of Ca
What does CIC-K6 do?
Brings Cl into the blood from the endothelium
What does NCX do?
Brings 3 Na into endothelium for 1 Ca into blood
What mechanisms does the cortical collecting tube have?
Aquaporin ROMK ENaC CLC Na pump
What does aquaporin do?
Allows water into blood
Why is it important that water is taken up in the kidney?
So it allows water to follow Na, maintaining blood pressure
What stimulates aquaporin?
Anti-diuertic hormone
What does ROMK do?
Allows K efflux into blood
What does ClC do?
Allows Cl into the blood
What does aldosterone do?
Upregulates ENaC, ROMK and the Na pump, leading to increase Na retention, and therefore increased water retention
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
How can aldosterone stimulated hypertension be treated?
Using spironolactone
What is spironolactone?
A mineralocorticoid receptor antagonist
What does spironolactone do?
Binds to aldosterone receptors, stopping the overexpression of these proteins
