Week 2 - Role of membranes as permeability barriers Flashcards
What is the relative permeability of a synthetic lipid bilayer to different classes of molecules?
- Hydrophobic molecules (O2, CO2, N2 and benzene) can diffuse
- Small, uncharged polar molecules (H2O, urea and glycerol) can diffuse
- Large, uncharged polar molecules and ions cannot diffuse through the phospholipid bilayer-
The permeability coefficients for most ions and hydrophilic molecules are very low (the transverse movement would require a large free energy change)
What does passive transport depend on?
- Permeability
- Concentration gradient
- The rate of passive transport increases linearly with increasing concentration gradient
How does water move across membranes?
By osmosis
- Most membranes are relatively permeable to water
What are the roles of transport processes?
- Maintenance of ionic composition
- Maintenance of intracellular pH
- Regulation of cell volume
- Concentration of metabolic fuels and building blocks
- The extrusion of waste products of metabolism and toxic substances
- The generation of gradients necessary for the electrical excitability of nerve and muscle
What models are there for facilitated transport?
- Protein pores (channels, may be opened in response to a stimulus)
- Carrier molecules (ping-pong, may be gated: ligand or voltage)
- Protein flip-flop (unlikely thermodynamically)
What is responsible for the transport of Cl- across the lipid bilayer?
Band 3 protein: it carries out a specific exchange of Cl-
What can increase the permeability of the lipid bilayer for polar substances?
The presence of specific proteins in the bilayer
Why is facilitated diffusion a saturable process?
- Each carrier can interact with only 1 or a few ions/molecules at any time
- There are a finite number of transporters present in the membrane
As the concentration gradient increases, a maximum rate of transport will be measured when all the transporters are busy
What determines where the transport of an ion/molecule is passive or active?
By the free energy change of the transported species
- This is determined by the concentration gradient for the transported species and/or by the electrical potential across the membrane bilayer when the transported species is charged
- Passive transport occurs spontaneously (e.g. simple and facilitated diffusion)
- Active transport requires energy
What is active transport?
Transport that allows the transport of ions/molecules against an unfavourable concentration and/or electrical gradient
- Energy directly/indirectly from ATP hydrolysis, electron transport or light is used
- Movement must be coupled with a thermodynamically favourable reaction
- Sometimes the transport of 1 substance is linked to the concentration gradient for another via a cotransporter (secondary active transport)
How can membrane transporters be driven?
By:
- Gradients of ATP
- Phosphoenolpyruvate
- Protons and sodium ions
- Light
- High-potential electrons
What are some co-transport systems?
Na+ - glucose:
- Symport
- Used in the small intestine and kidney
- Entry of sodium provides energy for the entry of glucose
Na+ - Ca2+ exchange:
- Inward flow of sodium down its concentration gradient drives outward flow of Ca2+ up its concentration gradient
- Antiport
Na+ - H+ exchange:
- Inward flow of sodium down its concentration gradient leads to cell alkalisation by removing H+
- Antiport
What is a uniport?
When 1 solute molecule species is transported from 1 side of the membrane to the other
What is a symport?
When the transfer of 1 solute molecule depends on the simultaneous or sequential transfer of a second solute in the same direction
What is an antiport?
When the transfer of 1 solute molecule depends on the simultaneous/sequential transfer of a second solute in the OPPOSITE direction
What is the free ion distribution of Na+ across the cell?
Intracellular conc = 12 mM
Extracellular conc = 145 mM
What is the free ion distribution of Cl- across the cell?
Intracellular conc = 4.2 mM
Extracellular conc = 123 mM
What is the free ion distribution of Ca2+ across the cell?
Intracellular conc = 10^-7 mM
Extracellular conc = 1.5 mM
What is the free ion distribution of K+ across the cell?
Intracellular conc = 155 mM
Extracellular conc = 4 mM
What is the sodium-potassium ATPase?
A pump
- Forms Na+ and K+ gradient
- Drives many secondary active transport process
- Uses ATP to pump ions
- 25% of the basal metabolic rate is used for the pump
- 3 Na+ out, 2 K+ in
What is the role sodium-potassium ATPase?
Drives many secondary active transport process:
- Ion homeostasis
- Intracellular Ca2+ ion concentration
- Intracellular pH
- Cell volume
- Ion gradients
- Nutrient uptake
What is the plasma membrane Ca2+ ATPase?
PMCA
- A primary active transporter
- Expels Ca2+ out of the cell
- Requires magnesium for ATP hydrolysis
- Transports H+ into the cell
- High intracellular calcium concentration is toxic cells
What is the sarco(end) plasmic reitculum ATPase?
SERCA
- Accumulates Ca2+ into the SR/ER
- High affinity, low capacity
- Removes residual calcium
What is the sodium-calcium exchanger?
NCX
- Secondary active transporter
- Low affinity, high capacity
- Removes most Ca2+
- Electrogenic (current flows in the direction of the Na+ gradient)
- Role in expelling intracellular Ca2+ during cell recovery
- Possible role in cell toxicity during ischaemia/reperfusion (reverses!)
- 3 Na+ in, 1 Ca2+ out
What is the sodium-hydrogen exchanger?
NHE
- Extrudes H+
- Involved in control of cell pH
- Exchanges extracellular Na+ for intracellular H+
- Electroneutral
- Regulates cell volume (Na+ has an osmotic influence)
- Activated by growth factors
- Inhibited by amiloride
What is the anion exchanger?
Cl-
- HCO3- exchanger
- Acidifies cell
- Removes base from cell
- Involved in cell volume regulation
Why do ion transporters work together in cell physiology?
By working together, they can achieve biological endpoints that would not be possible if they worked in isolation
How is the resting intracellular Ca2+ concentration controlled?
High intracellular Ca2+ concentration is toxic to cells so needs to be controlled: Primary active transport: - PMCA expels Ca2+ out of the cell - SERCA accumulates Ca2+ into the SR/ER Secondary active transport: - NCX expels Ca2+ Facilitated transport: - Mitochondrial Ca2+ uniparts (operate at high intracellular Ca2+ concentration to buffer potentially damaging Ca2+)
How is cellular pH controlled?
By the activity of a variety of plasma membrane transporters (after cellular buffering capacity has been exceeded)
- Acidification can be opposed by: expelling H+ ions, inward movement of bicarbonate ions
- Alkalisation can be opposed by: expelling bicarbonate via the anion exchanger
- Different ion transporters can also be used:
- – Acid extruders: Na+/H+ exchanger, Na+ dependent Cl-/HCO3- exchanger
- – Base extruders: anion exchanger
How is cell volume regulated?
Cells extrude ions in response to cell swelling and influx ions in response to cell shrinkage
- Water follows the ions
- Different cell types use particular combinations of transporters to achieve the regulation they need
What mechanisms are there to resist cell swelling?
- K+ and Cl- extruded via ion channels, so water moves out
- K+ and Cl- cotransported out, amino acids are moved out via sodium-potassium pump, so water moves out
- Anion exchanger moves Cl- in and HCO3- out, K+ is moved out in exchange for H+, H+ and HCO3- are combined to form H2CO3, CO2 is then released and water moves out
What mechanisms are there to resist cell shrinking?
- Na+ and Ca2+ move in via ion channels, so water moves in
- Na+ and Cl- move in together, Na+ and organic osmolytes move in together and K+, 2Cl- and Na+ move in together, so water moves in
- H2CO3 moves in via CO2 and is split into HCO3- and H+, HCO3- is moved out in exchange for Cl-, H+ is moved out in exchange for Na+
Describe renal bicarbonate reabsorption
Under normal circumstances, the kidney reabsorbs all of the bicarbonate filtered into the proximal tubule
- To retain base for pH buffers- Na+/K+ pump drives other channels by keeping intracellular Na+ concentration low, so NHE can pump H+ ions into the proximal tubule lumen
- H+ goes into the lumen to ‘pick up’ bicarbonate with HCO3 (as H2O and CO2) and bring it back into the cell
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
- Blood volume and therefore blood pressure falls
- Use diuretics to treat oedema or hypertension
