5 - Membrane Transporters 2 Flashcards
What is the role of the Na+/K+ ATPase transporter (antiporter)?
- Forms Na+ and K+ gradients to drive secondary active transport
- Contribute to -5mv of resting membrane potential
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What are some of the roles of secondary active transport?
- Regulate pH
- Absorption of nutrients like glucose
- Absorption of Na+ in the epithelia
- Regulation of cell volume and calcium conc
Why are high levels of calcium toxic to a cell?
Calcium would react with phopshate in the cytosol and form calcium phosphate which would calcify the cell
Why does calcium concentration in a cell have to be controlled?
- High levels toxic to cell
- Allows cell signalling if small changes in Ca conc
What is a semi-permeable membrane?
- A membrane that only allows select materials to diffuse through
What molecules can diffuse through a semi-permeable membrane directly?
- Small uncharged molecule
- Small hydrophobic molecules
H2O, O2, N2, CO2, Urea, Benzene, Glycerol
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What does the rate of passive transport depend on?
- Permeability coefficient (varies with each membrane, high number means more permeable)
- Concentration gradient
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Why does the model of rotating transport carriers not work in reality?
Proteins cannot flip-flop!!
What are some models of facilitated diffusion via proteins?
- Ping-pong (conformational change when molecules binds)
- LGIC (gated pores)
- VGIC
What are two examples of LGIC?
- Nicotinic acetylcholine
- ATP-sensitive K+ channel (normally open but when ATP is high it binds to channel and causes gate to close)
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What is an example of a VIGC and how does it work?
- Na+ channel
- Sensitive to membrane potential
- When membrane potential changes the gate opens as voltage sensors in the channel move up away from positive charge
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What is the difference between active and passive transport?
Active has positive free energy change and passive has negative free energy change
What two gradients affect passive transport?
- Electrochemical
- Concentration
Linear relationship with rate of transport
What is the general principles of active transport?
- Movement of ions or molecules against their concentration or electrochemical gradient
- Requires energy from ATP hydrolysis
- Cells use about 30-50% of their ATP for this
What sort of membrane protein do each type of molecule travel down?
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What are the concentrations of the four main ions intra and extracellularly?
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Is ATP synthase (F1F0) active or passive transport?
Active transport in reverse
What are the two types of co-transport?
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Why does the Na+K+ ATPase require energy?
- It is swapping charges but swapping three for two positive charges so needs energy to overcome this difference
What is the structure of the Na/K ATPase?
- P-type ATPase as phosphorylated on aspartate
- A-subunit (ATP, K, Na binding sites)
- B-subunit ( glycoprotein directs pump to surface)
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How is calcium moved out of the cell on the plasma membrane?
- PMCA (high affinity, low capacity)
- NCX (low affinity, high capacity, 2nd active transport)
NCX when calcium high, then PMCA
How does the Na+/H+ transporter work?
- Na pump sets up Na gradient
- Antiport
- Secondary active transport
- Entry of Na down it’s concentration gradient leads to cell alkalinisation by removing H+
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How does the Na/Glucose transporter work?
- Secondary active transport
- Symport
How do chloride ions normally get from the interstitium to the lumen, and what happens during cystic fibrosis?
- Transported in via Na+/2Cl-/K+ symporter down Na gradient
- CFTR passively transfers Cl- from in cell to lumen
- In CF, patient cant put as many CFTR proteins on membrane so less Cl- transported out of cell, less water leaves cell so sticky mucus
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What happens during cholera to cause diarrhoea?
- Toxin activates adenylate cyclase and therefore PKA
- PKA increases transport of Cl- by CFTR into the lumen
- More Cl- in lumen means more water so diarrhoea
What are the two primary active transport process involved in Ca regulation in a cell?
PMCA
Serca
When Ca is high in a cell, what else happens apart from removal out of cell and into SER?
- Facilitated diffusion by uniporters into the mitochondria
- Mitochondria act as buffers
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What happens to the NCX when the membrane is depolarised?
- Product inhibition by Na+
- Reverse mode of transport, Ca influx
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What happens to the NCX during ischaemia?
- Low O2 so ATP depleted
- Na pump inhibited
- Accumulation of Na in cell
- NCX reverse to remove Na
- Ca influx uncontrolled so cell dies due to toxicity
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How does a cell sort pH out when intracellular pH is too low?
- NHE
- NBC
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How does a cell sort the pH out when too high?
- Anion exchanger (band 3)
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What does NHE regulate and what is it activated and inhibited by?
- pH and cell volume
- Activated by growth factors (found in highly metabolic tissues)
- Inhibited by drug amiloride
What are all of the transportes involved in cellular pH regulation?
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How is the pH of a tissue defined?
On the type of transporters
Transporters set the set point and regulate the pH when it moves out of the set point
How do you regulate cell volume?
- Move osmotically active ions (Na,K,Cl) or AA
- Water will follow
- Electcroneutral transport
Cell shrinkage: influx ions
Cell swelling: remove ions
What are a few examples of transporter pairs involved in preventing cell swelling?
- Move ions without changing electrochemical gradient
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What are a few examples of transporter pairs involved in prevent cell shrinking?
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How and why is bicarbonate reabsorbed in the proximal tubule?
- Reabsorbed to retain a base in the blood that acts as a buffer to pH
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What are diuretics primarly used to treat and how do they work?
- Hypertension and Oedema
- Block transporters to prevent Na+ being reabsorbed into blood
- More Na+ excreted, therfore more water excreted
- Lowers blood volume
What are some common diuretics?
- Loop diuretics (thick ascending limb)
- Thiazides (DCT)
- Amiloride (DCT)
- Spironolactose
How do loop diuretics work?
- Inhibit NKCC2 so Na+ cannot be moved from filtrate to cells
- Occurs in thick ascending limb
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How do thiazides and amiloride work?
- In DCT
- Thiazides block NCCT
- Amiloride blocks ENaC
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What aldosterone do in the kidney?
- Mineralcorticoid hormone produced by adrenal cortex
- Acts as transcription factor when binding to its receptor
- Stimulates synthesis od ROMK, Na/K ATPase, ENaC
What is sprironolactone?
- Antagonist of mineralcorticoid receptor
- Therefore prevents production of ENaC, Na/K ATPase and ROMK
- Na cannot be reabsorbed so retained in collecting duct and so is water
What is hyperaldosteronism and how can it be treated?
- Body produces too much aldosterone which causes hypertension and low blood K levels
- Give amiloride and spironolactone which act in collecting duct
Why does drinking alcohol cause hyperosmotic urine?
- Alcohol suppresses pituitary from secreting ADH
- ADH normally acts on aquaporins so body can reabsorb water quickly
- No ADH, less aquaporins so not as much water reabsorbed
How do you raise intracellular Ca levels?
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How are sugars absorbed across the small intestine?
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How are amino acids absorbed in the small intestine?
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