Membrane Bilayer Flashcards
What are the 5 general functions of biological membranes?
- Continuous, highly selective permeability barrier
- Control of the enclosed chemical environment
- Communication
- Recognition - signalling molecules
i. adhesion proteins,
ii. immune surveillance - Signal generation in response to stimuli
(electrical, chemical)
What is the dry weight membrane composition?
– 40 % lipid
– 60 % protein
– 1-10 % carbohydrate
Membranes are hydrated structures, so what percent of total weight is water?
20%
Why is water important in the membrane?
Water is important to maintain the phospholipid bilayer as it ensures that the hydrophilic head are on the outside and the hydrophobic tails are on the inside.
What would happen to the membranes if the content of water is reduced?
If the water content is reduced, it could lead to slight deformation of the bilayer. It could also lead to changes in protein structure as it would affect the interactions of the protein leading to change in protein function
What does amphipathic mean?
contain both a hydrophilic and a hydrophobic moiety
Describe the structure of a phospholipid
Phospholipids comprise a fatty acid tail coupled via glycerol to a head group that contains phosphate and attached alcohol
What are the dominant phospholipids?
- Phosphatidylcholine 2.phosphatidylserine 3.phosphatidylenthanolamine
- phosphatidylinositol 5.phosphatidylgylcerol
What could the head groups on phospholipids be?
– range of polar head groups
– e.g. choline, amines, amino acids, sugars
What is the general length of fatty acid chain and which are most prevalent?
– Length between C14 and C24
– C16 and C18 most prevalent
What is sphingomyelin?
A related phospholipid in which glycerol has been replaced by a sphingosine
And the phosphocholine moiety has been replaced with a sugar (glycolipid). The alcohol group in sphingomyelin is choline.
What are glycolipids?
Sugar with lipid
What is the difference between cerebrosides and ganglioside Glycolipids?
– Cerebrosides – head group sugar monomer
– Gangliosides – head group oligosaccharide
sugar multimers
What are the 4 phospholipid motions?
- Flexion
- Rotation
- Lateral diffusion
- flip flop
What is the effect of saturated and unsaturated phospholipid fatty acid chains on the membrane fluidity/
Phospholipids with Saturated fatty acid chains pack very close together so the fluidity of the membrane decreases.
Phospholipids with unsaturated fatty acid chains have cis double bonds which introduces kinks which reduces phospholipid packing and therefore increases the fluidity of the membrane
For phospholipids, with unsaturated fatty acid chains how does mobility vary with length?
The longer the chain, the less it moves because more energy is needed to move the heavier chain.
In unsaturated fatty acids, the Cis double bond introduces a kink which deforms the phospholipid structure so reduces packing ability so makes it more fluid so phospholipids move more.
Why is easier for phospholipids to move by lateral diffusion that flip flop?
It is easier for a phospholipid to move by lateral diffusion than to flip flop because more energy is needed to flip flop because more forces need to be broken than moving laterallly
What are the 3 factors that affect membrane fluidity.
- Temperature
- Cholesterol
- Fatty acid chain
How does temperature affect membrane fluidity?
When the temperature is too low, the phospholipids have less energy so move less and pack more closely together in a rigid structure making the membrane less fluid.
When the temperature is too high the phospholipids have lots of energy so move a lot and pack less closely together, making the membrane more fluid.
What is the general function of cholesterol?
To stabilise the membrane
How does cholesterol affect membrane fluidity at low temperatures?
At low Temperatures, the bilayer is more rigid and packed more uniformly, but the cholesterol reduces phospholipid packing by inserting itself in the bilayer and increasing the distance between the phospholipids and thus increases fluidity.
How does cholesterol affect membrane fluidity at high temperature?
At high temperatures, cholesterol increases mass so heat distributed more so less effect of temp on the phospholipids.
At high temperatures, bilayer is more fluid so cholesterol reduces the fluidity and increases the rigidity by forming hydrogen bonds with the phospholipid bilayer and pulling the phospholipids closer together. Thus the membrane molecules are packed more closely. And having the sterol ring which is more rigid also helps to lower the membrane fluidity. Therefore the effect of high temperatures on the bilayer is reduced due to the cholesterol.
Describe the structure of cholesterol
Polar head group
Rigid planar 4 steroid ring structure
Non-polar hydrocarbon tail
How are cholesterols inserted into the phospholipid bilayer?
Molecules of cholesterol are immobilized against adjacent phospholipids through the formation of a hydrogen bond between the hydroxyl group of cholesterol and the carboxyl group of the phospholipid.
Describe the aspects of cholesterol’s paradoxical effect in phospholipid bilayer
Cholesterol reduces phospholipid packing by disrupting the uniform phospholipid bilayer structure so increases fluidity but it also reduces phospholipid chain motion which reduces fluidity. Therefore cholesterol maintains the fluidity of the membrane
What effect does cholesterol have on the permeability of membranes to water soluble molecules?
Cholesterol binds to the carboxyl group on the head of the phospholipid so makes the bilayer more rigid so makes it less fluid so mobility decreases so makes the bilayer more uniform and less permeable
What are the three lipids present in the membranes?
- phospholipids
- glycolipids
- Cholesterol
What is the evidence that proteins are present in the membranes?
Functional : The fact that all these are present in membranes indicates the presence of proteins: – Facilitated diffusion – Ion gradients – Specificity of cell responses
Biochemical
– Membrane fractionation + gel electrophoresis
– Freeze fracture
Describe how the proteins in erythrocyte membrane can be identified
- Eyrythrocytes Lysed and spun in a centrifuge to get a white pellet called the erythrocyte ghosts.
- The erythrocyte ghosts are then denatured and run through a polyacrylomide gel to perform electrophoresis
- The membrane is first put in a detergent which coats all the proteins in a negative charge which is attracted towards the positive electrode.
- Small proteins move faster and further, whereas the larger molecules move slowly and travel less
Give 6 proteins that are present in erythrocyte membranes
Spectrin a Spectrin b Band 3 Glycophorin Band 4.1 Actin
Describe how freeze fracture allows us to see membrane proteins
- Freeze cell or membrane so that everything is locked in position.
- A knife is used to press down on the ice crystal until it fractures at the points of weakness - between the two bilayer.
- Therefore fracture off the outside and inside lamella.
- Then we can do low angle shadowing using electron dense metal like osmium onto topography on membrane
- If protein sticking out, there will be a build p of osmium
- Then the preparation can be looked at in an electron microscope
What are the three modes of motion of proteins in bilayers?
- Conformational change
- Rotational
- Lateral
Which mode of motion is not permitted in proteins and why?
Flip flop because it is not thermodynamically possible as a lot of energy is required for the protein to flip flop and could result in breaking the membrane.
What restricts membrane protein mobility?
- Aggregates - membrane protein associations
- Tethering - association with extra-membranous proteins
(peripheral proteins), - both intracellular/extracellular proteins e.g. cytoskeleton or extracellular matrix - Interaction with other cells
- lipid mediated effects - proteins tend to separate out into the fluid phase or cholesterol poor regions
Describe peripheral membrane proteins
– Bound to surface
– Electrostatic and hydrogen bond interactions
– Removed by changes in pH or in ionic strength
Describe integral proteins
– Interact extensively with hydrophobic domains of the lipid bilayer
– Cannot be removed by manipulation of pH and ionic strength
– Are removed by agents that compete for non-polar interactions
E.g detergents and organic solvent
Describe the secreted protein biosynthesis
- Signal sequence on nascent polypeptide is recognised by the SRP
- SRP binds to the polypeptide and ribosome
- Translation halted by binding of SRP
- SRP recognised by SRP receptor/docking protein on ER membrane
- In making the interaction with the docking protein, the SRP is released from the signal sequence
- This removes the inhibitory constraint on translation so translation continues
- The signal sequence then interacts with a signal sequence receptor (SSR) within a protein translocator complex
- The ribosome becomes anchored to this pore complex, through which the growing polypeptide chain is extruded.
- The signal sequence is cut by the enzyme signal peptidase
- Once translation is finished, the ribosome is detached and goes back into the cytoplasm to find more mRNA
Describe the membrane protein biosynthesis
- Signal sequence on nascent polypeptide is recognised by the SRP
- SRP binds to the polypeptide and ribosome
- Translation halted by binding of SRP
- SRP recognised by SRP receptor/docking protein on ER membrane
- In making the interaction with the docking protein, the SRP is released from the signal sequence
- This removes the inhibitory constraint on translation so translation continues
- The signal sequence then interacts with a signal sequence receptor (SSR) within a protein translocator complex
- The ribosome becomes anchored to this pore complex, through which the growing polypeptide chain is extruded.
- The signal sequence is cut by the enzyme signal peptidase
- Protein synthesis is arrested by the stop transfer signal. The stop transfer signal is a hydrophobic sequence which forms the trans- membranous region of the protein. A lateral gating mechanism releases the membrane protein from the protein translocator into the lipid bilayer.
- The ribosome detaches from the ER and protein biosynthesis continues in the cytoplasm. The result is a transmembrane protein with its hydrophobic N-terminal directed in to the lumen and it’s hydrophilic C-terminal to the cytoplasm.
What percents of total body weight is water?
60%
What proportion of water in the body is in the ECF?
1/3
What proportion of water in the body is in the ICF?
2/3
What is ECF?
Fluid found outside cell membranes - fluid between cells
What is the ICF
Fluid inside cells bounded by the cell membrane
What compartments does the ECF divide into?
Interstitial fluid
Plasma
Lymph
Transcellular fluid
What proportion of ECF is interstitial fluid and plasma?
Interstitial fluid - 75%
Plasma - 25%
Describe the ion composition of the ECF and ICF
- The ECF has more Na+ than ICF
- The ICF has more K+ than ECF
- The ECF has more Cl- than ICF
- The ICF has more proteins than ECF
Which cation is the biggest proportion of the ECF?
Na+
Is the osmolality different in the ECF and ICF and why?
Not different because osmosis ensures equilibrium
Does changing ion conc by a little change osmolality?
No
Which substances can pass through the phospholipid bilayer?
- hydrophobic molecules
- small uncharged molecules - water, urea - not too well though
Which substances cannot pass through the phospholipid bilayer?
- Large uncharged polar molecules.
- ions
- charges polar molecules
Why can Na+ and K+ pass through the capillary wall but not the cell membrane ?
Na+ and K+ pass through the fenestrations in the capillary wall, not through the endothelium.
No fenestrations in the cell membrane so cannot pass through
Describe passive transport
- No energy needed
* Movement down concentration gradient
Describe active transport
- movement against concentration gradient
- requires ATP
Give examples of passive transport
- diffusion
- facilitated diffusion
- osmotic(and oncotic pressures) hydrostatic pressure
What are the examples of vesicular transport(active)?
- pinocytosis
- phagocytosis
What is diffusion
movement from
high ->low concentration
until equilibrium reached
What is flux?
Describes how fast a solute moves (i.e the number of moles crossing a unit area
of membrane per unit time (moles / cm2/ s)
What is flicks first law of diffusion?
The rate of flow of an uncharged solute due to diffusion is directly proportional to
the rate of change of concentration with distance in direction of flow.
How does membrane thickness affect flux?
If membrane is thinner, flux is faster
If membrane is thicker, flux is slower
How does surface area and thickness affect diffusion?
Diffusion is proportional to the surface area of he barrier and inversely proportional to its thickness
What is the driving force for net diffusion?
Concentration gradient
What happens when there is diffusion of 2 solutes?
Each substance diffuses down its own concentration gradient, independent of
concentration gradients of other substances
What is facilitated diffusion
Move from HIGH to LOW concentration through a protein channel
What are gated channels and give examples?
Proteins that open only in presence of stimulus (signal)
• stimulus usually different from transported molecule
• ex: ion-gated channels
• ex: voltage-gated channels
How do large molecules cross the membrane?
Exocytosis (out of cells)
• Moving large molecules into & out of cell requires ATP
• through vesicles & vacuoles
Endocytosis (into cells)
• phagocytosis = “cellular eating”
• pinocytosis = “cellular drinking”
• receptor-mediated endocytosis
How does water move through the membranes?
By osmosis Diffusion of water from high hypotonic solution to hypertonic solution • across a semi-permeable membrane
What happens if a cell is in a hypotonic solution?
Higher solute concentration inside than outside so water enters cell causing cell to swell and possibly burst
What happens if cell is in a hypertonic solution?
Higher solute concentration outside cell than inside so water moves out of cell causing it to shrink.
What is osmole?
The unit of osmolarity
What is the difference between osmolarity and osmolality
Osmolarity refers to the number of solute particles per 1 L of solvent
osmolality is the number of solute particles in 1 kg of solvent.
In a biological system, osmolarity and osmolality is the same but when measuring, it is always osmolality
In clinical practise what can b done to estimate serum osmolality
Serum osmolality can be estimated by doubling the serum sodium because osmolality is mainly determined by Na+ and Cl- in ECF
Describe hypertonic,hypotonic and isotonic
- Hypertonic - more solute, less water
- Hypotonic - less solute, more water
- Isotonic - equal solute, equal water
Water will move from hypotonic to hypertonic
What is osmotic pressure?
the pressure that would have to be applied to a pure solvent to prevent it from passing into a given solution by osmosis
Why is diffusion of water quicker in some cell membranes
Due to the presence of aquaporins which makes rapid diffusion of water possible
What are aquaporins/
• A channel for the transfer of water, and in some cases,
small solutes across the membrane (e.g. urea)
Aquaporin's are not ion channels but they are made up of 4 units (tetrameric)
Describe the aquaporin channel structure
• 6 transmembrane alpha helix proteins • Inner cavity is narrow and lined with hydrophilic AA • At the centre of the channel are (+) charged residues
Why is the positive charge inside aquaporins important?
• This prevent the movement of charge ions e.g. protons (H+) • Aquaporin's don’t disrupt H+ ion gradients in ATP production
How do aquaporins help water molecules to pass through the membrane?
• Water molecules LINE up one behind the other and pass single file through the hydrophilic channel • Movement still depends on solute concentration gradient this is still OSMOSIS
What is passive transport dependent on?
Permeability and concentration gradient
How does concentration gradient affect rate of passive transport?
Rate of passive transport increases linearly with increasing
concentration gradient
What are the 6 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 ion gradients necessary for the electrical
excitability of nerve and muscle
What are the models for facilitated transport?
Models for facilitated transport include protein pores (also known as channels), ping-pong proteins (carriers) and flip-flop proteins (unlikely thermodynamically).
What is the possible model of membrane transport proteins?
ping pong transport - through gated pore
- the substances bind to s specific site on the protein which causes a conformational change which results In the substance being released to the other side.
What are the 2 types of ion channels?
- Ligand gated ion channels
2. Voltage gated ion channels
Why is facilitated transport saturable?
Facilitated transport is a saturable process as each carrier can interact with only one or a few ions or molecules at any moment and a finite number of transporters are present in the membrane.
Thus, as the concentration gradient increases, a maximum rate of transport will be measured when all the transporters are busy.
How can we determine whether the transport of an ion or molecule is passive or active?
It is determined by the free energy change of the transported species. The free energy change is determined by the concentration gradient for the transported species and by the electrical potential across the membrane bilayer if the transported species has an ionic charge.
- If down conc/ electrical gradient, then free energy is -ve and transport is passive
- if against conc/electrical gradient, then free energy is +ve and transport is active
What is the free energy charge of a Passively transported molecule?
Negative
What is the free energy charge of an actively transported molecule?
Positive
What happens to the free energy change when the concentration gradient/ membrane potential difference is increased?
It increases
Ultimately what is the type of transport dependent on?
Concentration ratio and membrane potential
Where does the energy for active transport come rom?
directly or indirectly from ATP hydrolysis
What is the difference between the two types of ion channels?
Ligand gated ion channels - a ligand binds and causes a conformational change in the channel which results in it opening to allow the substance through or closing to stop the substance going through.
Voltage gated ion channels - open and close in response to the voltage potential difference across the membrane
What is the value of Na+ inside and outside the cell?
12mM inside
145mM outside
What are the values of K+ inside and outside cell?
155mM inside
4+mM outside
What are the values of Cl- inside and outside cell?
4.2mM inside
123mM outside
What are the values of Ca2+ inside and outside cells?
10^-7 mM inside
1.5mM outside
What are primary active transporters and give an example?
Transporters that directly takes ATP into an active site to hydrolyse it to ADP and bring about a conformational change.
An example is plasma membrane calcium ATPase (PMCA)
What is an example of a transporter which uses active transport in reverse mode and how does it work?
ATP synthetase- used in oxidative phosphorylation in mitochondrial membrane
Uses a gradient to drive ATP synthesis
What is cotransport?
More than one type of ion or molecule may be
transported on a membrane transporter per reaction cycle
What is uniport?
When 1 ion or molecule is transported through a transporter
What is symport
When two ions or molecules are transported down a transporter in the same direction
What is antiport?
When two ions or molecules are transported in opposite directions
Describe the task of the Na+ K+ ATPase (sodium pump)
It is an antiport co transporter which pumps 3 Na+ outside the membrane and 2 K+ inside the membrane using ATP and thus called active transport.
Why is the Na+ K+ ATPase very important in membrane?
VERY important for generating the ion
gradients that are used to allow
secondary active transport and action
potentials.
Only small contribution to resting
membrane potential
Why is the sodium pump called a P-type ATPase?
Because the phosphate released from ATP hydrolysis is transferred to the protein, causing a conformational change.
In the sodium pump, what is the function of the alpha subunit?
K+, Na+, ATP, ouabain binding sites
In the sodium pump, what is the function of the beta subunit?
glycoprotein directs pump to
surface
Is the Ca2+-Mg2+-ATPase a primary active transporter or secondary active transporter and why?
The Ca2+ Mg2+ ATPase is a primary active transporter as it directly uses ATP hydrolysis to pump Ca2+ ion through
Is the Na+-Ca2+-exchanger a primary or secondary active transporter and why?
The Na+ Ca2+ exchanger is a secondary active transporter because it does not use the energy from ATP hydrolysis directly, but uses the Na+ gradient created by the sodium pump. Movement of Na+ ions in, provides the energy to drive Ca2+ out of the cell
What is the function of the Cystic Fibrosis Transmembrane Lumen
Conductance Regulator
(CFTR)?
Transports Cl-ions outside the cell and into lumen in the lungs or gut or other areas with epithelial cells. This draws water out with it and ensures that mucus on the lumen surface is fluid.
What happens if the Cystic Fibrosis Transmembrane Lumen Conductance Regulator (CFTR) is non functional?
Fewer Cl- ions pumped out so less water follows so mucus on lumen surface becomes more thick
How does the Na+-glucose co-transporter work?
Entry of Na+ provides the energy for the entry of
glucose against concentration gradient (symport)
How does the Na+-H+-exchanger work?
Inward flow of Na+ down its concentration gradient
leads to cell alkalinisation by removing H+ (antiport)
How does the Na+-Ca2+-exchanger work?
Inwards flow of Na+ ions down the Na+ concentration
gradient drives the outward flow of Ca2+ up its concentration gradient (antiport)
What is the function of the Na+-K+-ATPase?
• Forms Na+ and K+ gradients • Drives Secondary Active transport – Control of pH – Regulation of cell volume and [Ca2+]i – Absorption of Na+ in epithelia – Nutrient uptake, e.g. glucose from, small intestine
Why is the intracellular levels of calcium very low?
High intracellular Calcium is toxic to cells.
Ensures calcium levels are very low to stop calcium phosphate forming
How can the very low levels of calcium be useful in cells?
Cells can use small changes in intracellular calcium as signals
What are the 4 transporters involved in control of resting Ca2+ concentration?
- Plasma membrane Ca2+-ATPase (PMCA)
- Na+- Ca2+-exchanger (NCX)
- Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)
- Ca2+- Ca2+ uniporters
What is the role of the Na+-Ca+-exchanger (NCX) in maintaining the resting Calcium concentration?
When the calcium ion concentration becomes high, the Na+-Ca+-exchanger (NCX) Exchanges 3 Na+ for 1 Ca2+ to expel the intracellular Ca2+ during cell recovery.
Possible role in cell toxicity during
ischaemia/reperfusion
What are the two features if the Na+- Ca2+-exchanger and how are they useful?
- Low affinity - so calcium ion concentration inside need to be quite high to be activated
- high capacity - can work efficiently and removes most Ca2+
What is the role of the Plasma membrane Ca2+-ATPase (PMCA)
In the maintenance of resting calcium ion concentration?
When the calcium levels are near resting calcium concentration, the PMCA expels Ca2+ out of the cell in exchange for a H+ ion. This is a primary active transporter
What is the role of the Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) in maintaining the resting calcium concentration?
SERCA accumulates Ca2+ into the SR/ER to remove it from the cytoplasm
What are the two features of PMCA and SERCA?
High affinity- a small change in calcium concentration can activate the transporters,
low capacity - only removes residual Ca2+
What is the role of the Mitochondrial Ca2+ uniports in maintaining the resting calcium concentration?
Operate at high [Ca2+] to buffer potentially damaging [Ca2+] - moves the Ca2+ ions into the mitochondria via facilitated diffusion
What is the activity of the Sodium Calcium Exchanger (NCX) dependent on ?
membrane potential
How does membrane potential affect the Sodium Calcium Exchanger (NCX) activity?
When the cell is polarised the exchanger pumps 3 Na+ in and pumps 1 Ca2+ out.
When the cell is depolarised, the inside is positive, therefore the sodium calcium exchanger reverses so that calcium is pumped in and 3 sodiums pumped out rather than the other way round
What happens to the Sodium Calcium Exchanger (NCX) in Ischaemia?
ATP depleted so the Na+-K+-ATPase inhibited so Na+ accumulates inside the cell causing the cell to become depolarises. This causes the NCX to reverse so that Na+ is pumped out and Ca2+ pumped in. The high Ca2+ inside cells is toxic.
How is the pH inside cells controlled?
By using transporters:
Acid extrudes and Base extrudes
Give two examples of acid extruders and explain how they work
- Na+/H+ exchanger - NHE - Uses inward sodium gradient to pump H+ out
- Na+-bicarbonate-chloride Cotransporter (NBC)
- uses sodium gradient to pump H+ out and HCO3- in. Na+ moves in and Cl- movies out as well
Give an example of a base extrudes and explain how it works
Cl-/HCO3- exchanger (anion exchanger)
- Uses Cl- gradient to move Cl- into cell and HCO3- out.
How does movement of ions affect cell volume regulation?
If cell swelling - extrude ions as water follows so cell returns to normal
If cell shrinking - influx ions so water enters to restore volume
Describe Bicarbonate reabsorption by the proximal tubule
The sodium potassium pump is used to pump sodium into the blood so that there is a lower concentration inside the proximal tubule cell. Sodium bicarbonate in the filtrate splits into sodium ions and bicarbonate ions. The sodium hydrogen exchanger uses the sodium ion concentration gradient to move sodium ions into the cell and protons into the lumen. The proton combines with the bicarbonate ion to make carbonic acid. The enzyme carbonic anhydride catalysed the breakdown of carbonic acid into carbon dioxide and water. The water and CO2 diffuse into the cell where carbonic anhydride catalyse the reaction of water and CO2 to make carbonic acid which splits into bicarbonate ions and protons. The bicarbonate ion is then picked up by the anion exchanger which uses the Cl- gradient to pump the bicarbonate ion into the blood.
Describe Na+ reuptake by the kidney in the thick ascending limb
The sodium potassium pump moves the sodium ions from the cell into the blood creating a concentration gradient so that sodium along with potassium and chloride can move into the cell from the filtrate through the sodium potassium 2 chloride cotransporter. The potassium and chloride ions are also moved into the blood via potassium chloride transporters. Potassium channels also moves some of the potassium back into the filtrate
What is the effect of loop diuretics in the thick ascending limb?
If the blood pressure is high, the drug loop diuretics will inhibit the sodium potassium 2 chloride cotransporter so that less absorption of ions into the blood so that less water would follow. Lower water content in blood results in lowered blood pressure.
Describe Na+ reuptake by the kidney in the distal convoluted tubule
The sodium potassium pump creates a sodium gradient. The sodium chloride cotransporter and epithelial sodium channel causes sodium to enter the cell . The chloride ions are transported into the blood via the potassium chloride exchanger and chloride channel.
What is the effect of thiazides in the distal convoluted tubule?
Thiazides - drug used to treat high blood pressure. Blocks sodium chloride cotransporter so fewer ions in the blood so less osmotic presssure so reduces blood pressure
What is the effect of amiloride in the distal convoluted tubule?
Amiloride - drug used to treat high blood pressure as it blocks the sodium channels so fewer sodium ions enter the blood so less water follows so lower osmotic pressure so lowered blood pressure
Describe the Na+ reuptake by the kidney in the cortical collecting duct
The sodium potassium ATPase creates a sodium concentration gradient causing sodium ions to enter the collecting duct cell via the epithelial sodium ion channel
What are present in the collecting duct membrane that increases the permeability of water
Aquaporins
Which hormone increases permeability by increasing the number of aquaporins present in the collecting duct?
ADH
What is the effect of the aldosterone hormone in the collecting duct?
The hormone aldosterone increases the expression of all the transporters so more sodium transported across the cell and into the bloods.
What is aldosteronism and how is it treated?
In individual with aldosteronism, they hyper secrete aldosterone so overexpresss the tranporters leading to enhanced sodium uptake so water follows leading to hypertension. This can be treated with amiloride or more commonly with spironolactone which block the aldosterone receptor so decreased expression of the tranporters
What is used to measure the membrane potential?
MICROELECTRODE
What is the membrane potential?
Membrane potential is the electrical charge that exists across a membrane (e.g. plasma membrane, mitochondrial membrane) and is always expressed as the potential inside the cell relative to the extracellular solution
What are membrane potential measure in?
millivolts (mV)
What is the range of membrane potentials in animals?
Animal cells have negative membrane potentials at rest that range from –20 to – 90 mV
What is the resting potential of Cardiac myocytes
-80mV
What is the resting potential of neurones?
-70mV
What is the resting membrane potential Skeletal muscle myocytes ?
-90mV
What is the eating membrane potential of Smooth muscle myocytes ?
-50mV
How is he resting membrane potential set up?
The chemical gradient of potassium causes it to move out of cells creating a negative membrane potential and the electrical gradient causes it to move in.
When the chemical gradient and electrical gradient are equal and opposite, there will be no net movement of K+,
but there will be a negative membrane potential
Thus the resting membrane potential arises because the membrane is selectively permeable to K+
Which channels dominate the membrane ionic permeability at rest?
Open K+ channels
What is the Nernst equation?
The Nernst equation allows you to calculate the membrane potential at which K+ will be in equilibrium, given the extracellular and intracellular K+ concentrations.
Why is the resting potential of skeletal muscle -90mV
Many Cl- and K+ channels open in resting membrane so membrane more polarised.
Define depolarisation
A decrease in the size of the membrane potential from its normal value Cell interior becomes less negative
Define hyper polarisation
An increase in the size of the membrane potential from its normal value Cell interior becomes more negative
How do membrane potential arise and how can it be changed?
Membrane potentials arise as a result of selective ionic permeability. Changing the selectivity between ions will change membrane potential. Potassium ion channels are always open and maintain the resting potential. Movement of other ions results in the change in membrane potential
What happens if your increase the membrane permeability to a particular ion?
Increasing membrane permeability to a particular ion moves the membrane potential towards the Equilibrium Potential for that ion
Opening which channels will cause hyperpolarisation?
K+ and Cl- channels
Opening which channels will cause depolarisation?
Na+ or Ca2+ channels
What does the contribution of each ion to the membrane potential depend on?
How permeable the membrane is to that ion
What are the 3 types of channels?
- Ligand gated channels
- Voltage gated channels
- Mechanical gated channels
How does the nicotine acetylcholine receptors work?
- Have an intrinsic ion channel
- Opened by binding of acetylcholine
- Channel lets Na+ and K+ through, but not anions
- Moves the membrane potential towards 0 mV, intermediate between ENa and EK
Describe how ligand gated channels work and give examples
The channel opens or closes in response to binding of a chemical ligand e.g. Channels at synapses that respond to extracellular transmitters
c. Channels that respond to intracellular messengers
Describe how voltage gated channels work and give examples
Channel opens or closes in response to changes in membrane potential
e.g. Channels involved in action potentials
Describe how mechanical gated channels work and give examples
Channel opens or closes in response to membrane deformation e.g. Channels in mechanoreceptors: carotid sinus stretch receptors, hair cells
What happens at synapses?
At the synapse, a chemical transmitter released from the presynaptic cell binds to receptors on the postsynaptic membrane
How can you distinguish Fast and Slow synaptic transmission?
In fast synaptic transmission, the receptor protein is also an ion channel.
Transmitter binding causes the channel to open.
In slow synaptic transmission The receptor and channel are separate proteins.
Describe how excitatory synapses work
Excitatory transmitters open ligand-gated channels that cause membrane depolarization. Can be permeable to Na+, Ca2+, sometimes cations in general (nAChR)
What is the change in membrane potential at excitatory synapses called?
Excitatory post-synaptic potential (EPSP)
What are the two features of Excitatory post-synaptic potential (EPSP)
- Longer time course than AP
2. Graded with amount of transmitter
Give two examples of excitatory transmitters
Acetylcholine, Glutamate
Describe how inhibitory synapses work?
Inhibitory transmitters open ligand-gated channels that cause hyper polarisation. Permeable to K+ or Cl-
Give two examples in inhibitory transmitters
Glycine, g-aminobutyric acid (GABA)
Give two examples of slow synaptic transmission
- Direct G-protein gating
2. Gating via an intracellular messenger
What are two other factors that influence membrane potential?
- Changes in ion concentration
2. Electrogenic pumps
What are lectrogenic pumps and how do they influence membrane potential?
Na/K- ATPase
• One positive charge is moved out for each cycle
• In some cells, this contributes a few mV directly to the membrane
potential, making it more negative
• Indirectly, active transport of ions is responsible for the entire
membrane potential, because it sets up and maintains the ionic
gradients
Describe direct g-protein gating
When ligand binds , activates a transducing protein which diffuses through membrane to an effector which is a channel protein.
Localised
Quite rapid
Describe Gating via an intracellular messenger
Receptor activated, G protein diffuses to an effector which is the enzyme which produces a substance that takes message through cell to channel. Usually a protein kinase is activated - phosphorylation of target channel
