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56 Cards in this Set
- Front
- Back
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List the main kinds of lipids and general properties of fatty acids.
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Main kinds of lipids:
Phospholipids ( predominant), plasmalogens, glycolipids, cholesterol. Fatty acids: - Fuel molecules - Long straight hydrocarbon chains with an even number of Carbon atoms - C16 & C18 are the most prevalent - Cis unsaturated double bonds introduce a kink in the chain, reducing phospholipid packing and increasing fluidity - Cis double bonds decrease the ability of phospholipids to form 2D crystals. - Increase in temperature, increases kinking. |
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Describe phospholipids and plasmogens.
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Phospholipids ( predominant lipids)
- eg phosphatidylcholine - Glycerol backbone - 2 fatty acids chains at C1 & C2 of glycerol - Phosphate group (-ve) attached to C3 - Polar head group attached to phosphate group – eg choline, amine, amino acid, sugar Plasmalogens - Phospholipid where C1 fatty acid is replaced by an aldehyde group. - Found in myelin sheaths, sarcolemmas - Sphinomyelin is the only phospholipid not based on glycerol backbone |
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Describe glycolipids and cholesterol
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Glycolipids
- Replace phosphate group + head group of a phospholipid with a sugar - Cerebrosides – head group sugar monomers - Gangliosides – head group oligosaccharides Cholesterol ( 50 % of total membrane lipid) - Polar head group ( OH group hydrogen bonds to double bonded oxygen in ester bond of phospholipid) - Rigid planar steroid ring structure – restricts motion of fatty acid chain preventing kinking, thus reducing fluidity. - Non polar hydrocarbon tail - The role of cholesterol is the maintain membrane structure by preventing the extremes of crystallisation or fluidity. - 1.1 ratio of phospholipids to cholesterol in membranes - Cholesterols lie next to phospholipids and thus reduce phospholipid packing, increasing fluidity of membrane. |
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Describe the properties of amphipathic molecules and explain the process of formation of lipid bilayers
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Amphipathic molecules have hydrophilic and hydrophobic moieties and can form micelles or bilayers in water.
For phospholipids and glycolipids, bilayer structures are favoured in water and are formed spontaneously driven by van der waals forces between hydrophobic tails. Bilayers are stabilised by electrostatic and hydrogen interactions. |
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Discuss the functions of the plasma membrane.
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- Continuous, highly selective permeability barrier
- Control of the enclosed chemical environment - Communication – - Recognition ( signalling molecules, adhesion proteins, immune surveillance) - Signal generation in response to stimuli Different regions of the plasma membrane have different functions such as interaction with basement membrane (integrins), interaction with adjacent cells( cadherins and catenins), transport, absorption, secretion, signal conduction, synapses. |
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Distinguish peripheral from integral membrane proteins and explain the forces associating them with the membrane
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Peripheral proteins are attached to the surface by electrostatic interactions, hydrogen bonds and disulphide bonds. They can be removed from a membrane bilayer fraction by modification of pH or ionic strength.
Integral proteins form extensive hydrophobic interactions with hydrophobic regions of the membrane. They can be removed by chemicals which compete for the hydrophobic regions such as organic solvents or detergents. Integral proteins may be transmembranous. |
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Describe transmembrane domains.
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Transmembrane domains are usually made of 18-22 amino acids and are often alpha helical and contain mostly amino acids with hydrophobic R groups. All small hydrophobic amino acids favour alpha helices except proline which causes kinks as it lacks OH group for H bonds and glycine which is very small and flexible and so favours other structures.
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Describe in general terms the mechanism of membrane insertion of integral proteins and the features of these proteins which explains their topology in the membrane. Discuss membrane asymmetry
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Proteins destined for a membrane have a stop transfer signal sequence which arrests the passage of the protein through the membrane. The stop transfer signal is region of 18-22 highly hydrophobic amino acids which is followed on the C terminal side by 2 basic amino acids ( charged). Asymmetrical orientation of membrane proteins is directed by protein synthesis and is important for function ie if the protein is a receptor it must be positioned at the correct surface.
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Discuss the influence of unsaturated fatty acids and cholesterol on membrane fluidity.
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Unsaturated fatty acids form cis double bonds which introduce a kink in the phospholipid, causing reduced packing and increasing fluidity. Cholesterol stabilises the membrane by preventing the extremes of crystalisation and fluidity. Cholesterol and phospholipids are present in equal amounts in the membrane. Cholesterol has an OH group which forms hydrogen bond with the O in the ester group on a phospholipid. It reduces packing of phospholipids and prevents kinking of the fatty acid tail, thus reducing fluidity.
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6. Describe the main features of the fluid mosaic model of membrane structure and explain the restrictions on protein movement in the membrane, including potential interactions with cytoskeletal elements.
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The plasma membrane is composed of 60% protein, 40% lipid, 1-10% carbohydrate (dry weight)
The plasma membrane is hydrated so 20% of weight is accounted for by water. Phospholipid motions: 1. Intra chain motion ( flexion – kink formation) 2. Fast axial rotation 3. Fast lateral diffusion along same plane of bilayer 4. Flip flop – exchange of lipids from one half of the bilayer to the other. -REQUIRES LOTS OF ENERGY Proteins carry out many important functions in plasma membrane such as enzymes, transporters, pumps, ion channels, receptors and energy transducers. Protein motion: 1. Conformational change 2. Rotational 3. Lateral diffusion – proven by florescence recovery after bleaching CAN’T FLIP FLOP – too large and for glycoproteins the hydrophilic carbohydrate chain locks orientation of protein in plasma membrane. |
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What restricts protein motion?
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Protein motion restrictions:
- Lipid mediated effects – proteins tend to separate out into the fluid phase or cholesterol poor regions. - Membrane protein associations - Association with extra-membranous proteins eg cytoskeleton. |
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Describe the erythrocyte membrane and cytoskeleton
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The erythrocyte membrane has over 10 major proteins of which most are peripheral. Protein bands 3 and 7 are integral glycoproteins. The carbohydrate chains are hydrophilic and so prevent flip flop and lock in orientation of protein.The erythrocyte cytoskeleton comprises of a network of spectrin and actin molecules. Spectrin is a long, floppy rod like molecule which forms heterotetramers of alpha2 and beta2 ( subunits). Other peripheral proteins involved are adducin, band 4.1 and ankyrin.
The integral membranes proteins, band 3 – anion exchanger and glycophorin A , attach to the cytoskeleton and this restricts the lateral mobility of the membrane protein. |
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Describe hereditary spherocytosis and hereditary elliptocytosis.
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The erythrocyte cytoskeleton is needed to maintain the deformability necessary for erythrocytes to squeeze through capillaries without undergoing lysis. The following diseases of the cytoskeleton prevent this function and so causes haemolytic anaemia – rate of haemolysis is greater than production.
Hereditary spherocytosis: - 40-50% of spectrin is depleted - RBCs round up and become less resistant to lysis - Cleared by spleen Hereditary elliptocytosis: - Defect in spectrin - Unable to from heterotetramers - Fragile elliptoid cells formed. |
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List H2O, O2, H+ and glucose in descending order of permeability of synthetic lipid membrane to molecules:
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- Hydrophobic molecules ( O2, CO2, N2, benzene)
- Small uncharged polar molecules ( H2O, urea, glycerol) - Large uncharged polar molecules ( glucose, sucrose) - Ions ( H+, Na+,K+, etc) |
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Define Passive transport:
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It is the spontaneous movement of molecules down a concentration gradient without the need of energy. Passive transport is dependent on permeability and concentration gradient. The rate of passive transport increases linearly with increasing concentration gradient.
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How can membrane permeability vary?
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Membrane permeability can vary greatly depending on their composition and the proteins which are expressed. For example an erythrocyte membrane is more permeable to glucose than others as it has more GLUT 4 receptors expressed. If the membrane is excited or rested it will vary their permeability to potassium and sodium ions.
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List roles of transport processes:
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- Maintenance of ionic composition - electroneutral
- Maintenance of intracellular Ph – acid and base extruders - Regulation of cell volume – combination of many transport systems - Concentration of metabolic fuels and building blocks – sodium concentration powers glucose uptake in intestinal cells and renal proximal tubules - The extrusion of waste products of metabolism and toxic substances - The generation of ion gradients necessary for the electrical excitability of nerve and muscle – influx of calcium |
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Define facilitated transport and describe models of facilitated transport
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Facilitated transport is diffusion down a concentration gradient via proteins such as protein pores ( channels) or carrier molecules (ping pong) or ligand Gated ion channels, voltage gated ion channels, gap junctions (connexion) – closed when cellular calcium rises above 10micromoles.
- Binding of molecule to protein causes a conformational change - Transferring of molecule across protein - Releasing into cystolic or extracellular space The rate of diffusion of molecules is dependent on how fast conformational change can occur and how many specific protein channels there are in the membrane. |
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What determines the free energy change of a transported species.
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Free energy change is determines by the concentration gradient for the transported species and by the electrical potential across the membrane bilayer when the transported species is charged. The free energy change of the transported species determines whether transport is spontaneous ( passive transport) or requires
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Define active transport.
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Active transport is the movement of molecules against the concentration gradient or electrical gradient and requires energy directly or indirectly from the hydrolysis of ATP, electron transport or light.
Primary active transport uses energy directly from the hydrolysis of ATP eg PMCA and Na+/K+/ATPase Secondary active transport is where the transport of one substance is linked to the concentration gradient for another via a co-transporter eg NCX. the hydrolysis of ATP is used indirectly. Some cells spend up to 30-50% of their ATP on active transport |
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List some co-transport systems.
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- Na+ glucose co-transport system of the small intestine and kidney ( symport). Entry of sodium provides the energy for the entry of glucose.
- NCX –Na+ - Ca2+-exchanger(antiport): inward flow of sodium ions, down its concentration gradient drives the efflux of calcium ions down its concentration gradient – 3Na+ for Ca2+ - NHE- Na+-H+-exchange (antiport): inward flow of sodium down its concentration gradient leads to cell alkalization by removing H+. |
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Define the different types of transporters.
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Uniport: one solute molecule species is transferred from one side of the membrane to the other
Cotransporters: - Symport: when the transfer of one solute molecule depends of the transfer of a second solute molecule in the SAME direction eg Na+-glucose co-transport - Antiport: when the transfer of one solute molecule depends on the transfer of a second solute molecule in the OPPOSITE direction eg NCX |
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Outline the major physiological roles and structure of sodium- potassium pump
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Na+-K+-ATPase:
- primary active transporter which drives many secondary active transport systems including calcium homeostasis, pH regulation, cell volume regulation, resting membrane potential, nutrient uptake. - Pumps 3 Na+ out for 2 K+ inwards – electrogenic Functions: establishes sodium and potassium gradients, can act in reverse to generate ATP, only generates 5mv towards resting membrane potential (mainly voltage sensitive K channels) Structure: - P-type ATPase –phosphorylated on aspartate - Alpha subunit – binding site for potassium, sodium and ouabain (inhibitor) - Beta subunit – glycoprotein orientates protein |
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Outline the major physiological roles of sodium hydrogen exchange and anion exchange.
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NHE – secondary active transport.
- Antiport - 1 Na+ in for 1 H+ out – alkalization pH regulation – electroneutral - Regulates cell volume - Growth factors activate transport – metabolically active cells produce more H+ - Inhibited by amiloride on cardiac cells to minimise repurfusion injury ( but mainly work to inhibit ENAC on distal convoluted tubule) Anion Exchange - eg band 3 in erthyrocyte membrane - Cl- in for HCO3- out - Acidification and alkali extrusion - Ph regulation - Cell volume regulation |
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Outline the major physiological roles of plasma membrane calcium ATPase, sodium calcium exchange and sarco(endo)plasmic reticulum ATPase.
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PMCA:
- Primary active transport - Calcium out of cell – regulates resting calcium levels - High affinity low capacity NCX: - Secondary active transport - antiport - 3Na+ in for Ca2+ out – electrogenic - Low affinity high capacity - Regulates resting calcium levels BUT when depolarised reverses -> influx of calcium SERCA: - Primary active transport - Calcium into SR/ER -> binds to buffering proteins eg calsequestrin, calbindin,parvalbumin - high affinity, low capacity |
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Describe the clinical implications of the CFTR protein ( cystic fibrosis transmembrane conductance regulator protein)
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CFTR protein pumps out chlorine ions and water then follwos
Cystic fibrosis: - faulty CFTR protein in epithelia - chloride ions stay in cell and so does water - respiratory tract: thick, vicous mucous develops -> infections - GI tract: steatorrhea, harder to pass faeces, less lubrication, malabsorbtion - Pancreas: duodenum blocked by mucus -> no passage of digestive enzymes to small intestine -> steatorrhea and malabsorption - Enzymes given after meals, DNAase aerosol spray to break up bacteria in mucous, massage to remove mucous, antibiotics Diarrhoea by cholera - Protein kinase A is activated by cholera and phosphorylates CFTR so it is activated and removes excess chloride ion, causing a very water secretion in the bowels -> diarrhoea |
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How is cell volume regulated?
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Cell volume is regulated by ion transporters working together in an electroneutal fashion. Every cell has a different group of transporters and so regulation varies between every cell.
Cell swelling and shrinking is due to changes in extracellular or intracellular osmotic pressures. Cell swelling is opposed by pumping osmotically active ions out of the cell and water then follows. Cell shrinking is opposed by pumping osmotically active ions in to the cell and water then follows. These mechanisms can only work if the patient is well hydrated. The main transporters involved are Na+-K+-ATPase and Anion Exchanger. |
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How is pH regulated?
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Na+-K+-ATPase – provides sodium gradient to provide indirect energy to drive all the following transporters.
Acid extruders(pump H+ out or pump HCO3- in - NHE – H+ is pumped out - Na+-Cl- - H+- HCO3- co transport – chloride and hydrogen ions out, bicarbonate and sodium ions in Alkali influx - Na+-Cl- - H+- HCO3- co transport – chloride and hydrogen ions out, bicarbonate and sodium ions in ( alkali influx and acid extrusion) - Na+-3HCO3- co-transport – symport all in Alkali extruder - Anion Exchange –Cl- ion and HCO3- out |
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Describe how ion channels work together in the kidney and describe how drugs may be used to treat oedema or hypertension.
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The ion channels work together in the kidney to achieve a physiological endpoint that would not be possible if they work in isolation.
Under normal circumstances all bicarbonate ions are reabsorbed in the proximal tubule of the kidney. This is in order to retain ph buffer. Nearly all sodium ions in the glomerular filtrate are reabsorbed. This is due to the low intracellular [Na+] in the tubular cells, achieved by the Na+-K+-ATPase. Fluid loss is required to treat oedema and hypertension and this can be achieved by blocking one or more of the Na+ reabsorbtion mechanisms with diuretic drugs. This increases Na+ excretion to produce a hyperosmotic urine and hence excretion of water. Thiamzide -> Na+/Cl- cotransporter -> distal convoluted tubule Loop diuretic -> Na+-K+¬-2Cl- cotransporter -> proximal tubule Spironolactone -> ROMK, Na+ -K+-ATPase -> cortical collecting duct Amiloride -> epithelial sodium channel -> cortical collecting duct |
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Describe the use of cardiac glucosides
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Cardiac glucosides eg digoxin and ouabain (bind to alpha subunit) inhibit sodium, potassium pump so that ATP levels decrease, sodium accumulates in the cell and secondary transporter NCX is reversed and calcium enters the cell. The SR absorbs excess calcium from the sarcoplasm and so on stimulation from following action potential, more calcium is released into sarcoplasm and so muscle contraction is more forceful and faster.
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State the values of free intracellular and extracellular ion concentrations of calcium, chlorine, sodium and potassium.
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Intracellular:
- Sodium = 12mM - Potassium= 155mM - Calcium = 10-7M - Chlorine = 4.2mM Extracellular - Sodium = 145mM - Potassium = 4Mm - Calcium = 1.5mM - Chlorine = 123mM |
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Outline what a membrane potential is, how the resting potential of a cell may be measured and the range of values found.
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All cells have an electrical potential difference across their plasma membrane. Changes in this membrane potential underlie the basis of signal transmission in the nervous system and in many cells. Membrane potentials are expressed as the voltage inside of the cell relative to the outside. They are set up because the membrane is selectively permeable to different ions.
The resting potential of cell can be measuring using a microelectrode ( a fine glass pipette). The resting potential is always negative inside the cell from -20 to – 90mV. Cardiac and skeletal muscle cells have the largest resting potentials of -80 to -90mV. Nerve cells have resting potentials between -50 and -75mV. . |
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Understand the concept of selective permeability and explain how the selective permeability of cell membranes arises.
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The permeability of the membrane to ions occurs due to presence of channel proteins.
The ion channels are characterised by: - Selectivity – the channel lets through only one or a few ion species eg channels selective for Na+, K+, Cl-,Ca2+. - gating : the channel can be open or closed by a conformational change in the protein molecule - a high rate of ion flow that is always down the electrochemical gradient for the ion. The permeability of a membrane to an ion depends on the number of selective ion channels that are open. The membrane potentials are set up because the membrane is selectively permeable to different ions |
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Describe how the resting potential is set up given the distribution of ions across cell membranes
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The Na+-K+-ATPase generates the sodium and potassium gradients:
- a high intracellular [K+] = 160mV and a low extracellular [K+] = 4.5mV - A low intracellular [Na+] = 10mV and a high extracellular [Na+] = 145Mv At rest, the K+ channels are open and so potassium moves down its concentration gradient, out of the cell. As anions cannot follow, the cell will become negatively charged inside. The membrane potential will oppose the outward movement of K+ and the system will come into equilibrium. The resting membrane potential is never Ek because other types of channel are also open. |
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Understand the term equilibrium potential for an ion and calculate its value from the ionic concentrations on either side of the membrane.
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The equilibrium potential for an ion is the membrane potential at which there is no net movement of the ion.
The Nernst equation calculates the equilibrium potential for an ion. Eion = 61/z log10 [ion]out/[ion]in Z = valency = charge of ion Example: calculating EK [K+]OUT = 4.5ml [K+]IN= 160ml EK = 61log10 [4.5]/[160] = -95Mv Increasing the permeability of the membrane for an ion will shift the membrane potential towards the equilibrium potential for that ion, thus opening Na+ and Ca2+ channels depolarises the membrane. Opening K+ and Cl- channels hyperpolarises the membrane. Hyperkalacaemia : Increasing extracellular potassium concentration depolarises membrane eg increase intracellular K+ concentration to 10m, EK = -73mv |
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Define depolarisation and hyperpolarisation and explain the mechanisms that may lead to each of these.
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Depolarisation = a decrease in the membrane potential so that the inside of the cell becomes more positive, less negative
- Opening Na+ or Ca2+ channels Hyperpolarisation = an increase in the membrane potential so that the inside of the cell becomes more negative. - Opening K+ or Cl- channels |
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What is the GHK equation?
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The GHK equation ( goldman-hodgkin-katz) approximates the membrane potential, using the relative permeabilities of the ions involved.
Membrane potential = 61/z log10 (PNa[Na]out + Pk[K]out+PCl[Cl-]out ( PNa[Na]in+Pk[K]¬in+PCl[Cl-]in P = relative permeability of the ion Eg if it is 20 times easier for K+ to cross as Na and Cl then the PK=20 |
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Explain how changes in ion channel activity can lead to changes in membrane potential and outline some of the roles of the membrane potential in signalling within and between cells
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Increasing membrane permeability to a particular ion moves the membrane potential towards the equilibrium potential for that ion.
EK = -95mV ENa= +70mV ECl = - 96mV ECa= +122mV Depolarisation: more positive membrane potential eg a change from -70mV to -50Mv - Opening Na+ or Ca2+ channels will cause depolarisation Hyperpolarisation: more negative membrane potential eg a change from -70 to -90mV - Opening K+ or Cl- channels will cause hyperpolarisation Changes in membrane potentials underlie many forms of signalling between and within cells 1. Action potentials in nerve and muscle cells 2. Triggering and control of muscle contraction 3. Control of secretion of hormones and neurotransmitters 4. Transduction of sensory information into electrical activity by receptors 5. Postsynaptic actions of fast synaptic transmitters |
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Describe gating mechanisms.
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Gating mechanisms open or close channels and so, control channel activity.
Ligand gating - Channel opens and closes in response to binding of a chemical ligand - Found at synapses where they respond to extracellular transmitters eg ACh - Channels that respond to intracellular messengers Voltage gating - Channels open and close in response to membrane potential - Channels involved in action potentials eg sodium pump Mechanical gating - Channels open or close in response to membrane deformation - Eg channels in mechanoreceptors: carotid sinus stretch receptors, hair cells |
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Outline how ligand gated channels can give rise to synaptic potentials.
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Ligand gated channels are involved in fast synaptic transmission.
Depolarising transmitters eg Ach and glutamate open channels which are sensitive to Na+, Ca2+ and other cations. This causes depolarisation of the membrane potential – an excitatory postsynaptic potential (EPSP). Hyperpolarising transmitters eg GABA ( gamma aminobutyric acid) and glycine open channels which are sensitive to K+ and Cl¬- ions. This causes hyperpolarisation of the membrane potential – an inhibitory postsynaptic potential (EPSP). Ach receptors are ligand gated ion channels that allow the passage of K+ and Na+ ions, achieving a membrane potential towards 0mv, which is the middle of EK and ENa. Slow synaptic potentials involve GPCR eg muscarinic receptors in parasympathetic innervations. |
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What are the effects of hyperkalaemia?
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Hyperkalaemia increases the EK making it more positive so that membrane is more depolarised.
In cardiac muscle cells this increased depolarisation makes it easier for action potentials to be generated and ectopic arrthymias arise. In pacemaker cells, the funny channels work best at negative potentials and so the leak of sodium and potassium is much slower and takes longer to depolarise membrane to threshold. This results in slower heart rate. |
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List the characteristics of an action potential and describe temporal and spatial summation.
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- Change in membrane potential
- All or nothing response – either passes the threshold level or doesn’t Increase in frequency -> pain - Depends on ionic gradients and relative membrane permeability - Propagated without loss of amplitude – same pattern along membrane Temporal summation: occurs in a single neuron where there is a high frequency of potentials. The new potential starts before the previous potential has finished and so they summate to form greater depolarisation that reaches the threshold potential Spatial summation: excitatory postsynaptic potentials from different nerve cells summate to reach threshold potential. |
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Describe the change in membrane potential that occurs during an action potential
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Depolarisation along a membrane causes opening of voltage gated sodium channels. The sodium enters the cell and accumulates, further depolarising the membrane and triggering more sodium channels to open by positive feedback. The threshold level is reached and the sodium channels become inactivated and the voltage gated potassium channels open to repolarise the membrane. As the membrane potential decreases, the sodium channels are closed. Hyperpolarisation of the membrane then resets the sodium channels and they are de-inactivated, and can be opened again in response to depolarisation.
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Outline the structure of voltage activated ion channels
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Na+ channel ( similar to VOCC)
- Only 1 type - 4 repeated 6 transmembrane domains – released as 1 protein from golgi - S1-S6 x 4 - s4 is a voltage sensor, with positive amino acids contributing to voltage sensitivity. It forces conformational change of protein to open or close pore - Region between S5 and S6 is pore forming region - selectivity - Inactivation particle, between S6 and S1 of adjacent repeat, plugs the pore – hyperpolarisation opens the pore K+ channel: - Many different types as made by different subtypes ( respond to different chemicals, perform different functions) - one 6 transmembrane domain protein released from golgi - Same structure as Na+ channel except each repeat is a separate subunit - Don’t have inactivation particle |
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Explain the basis of refractoriness in nerve and muscle
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The absolute refractory period is the period immediately following an action potential when it is absolutely impossible to generate another action potential. This is because all of the sodium channels are inactivated and it takes time for the membrane to repolarise and reset the sodium channels. Absolute refractory period ensures propagation of action potential along axons in nerve cells can only occur in one direction.
The relative refractory period is the period after the ARP where an action potential may be possible to generate but a larger stimulus will be needed. This is because some sodium channels with be de-inactivated. |
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Define accommodation
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An increase in the threshold level for an action potential to be generated, that occurs during prolonged stimulation.
The longer the stimulus, the larger the depolarisation needed to initiate an action potential as sodium ions accumulate in the cell, increasing the threshold level. Thus as stimuli intensity increases, the threshold level increases until eventually the sodium channels open, activate and inactivate before the threshold potential is reached. Therefore no action potential is generated. |
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Explain how local anaesthetics act
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Local anaesthetics such as lidocaine and procaine block voltage gated sodium channels in their open and inactive states and dissociate before next action potential arises and so prevents generation of premature action potentials. They are given to treat arrhythmias.
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1. Describe the results of extracellular recording and how this can be used to measure conduction velocity
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Electrodes are used to initiate an action potential. Conduction velocity can be calculated by measuring the distance between the stimulating electrode and the recording electrode and the time gap between the stimulus and the action potential being registered by the recording electrode.
Conduction velocity = distance/time |
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Explain how axons are raised to threshold
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A change in membrane potential in one part of the axon can spread to adjacent areas of the axon by local current spread and if depolarisation to threshold is reached then an action potential is initiated in that region.
The further the local current spreads, the faster the conduction velocity of the axon. Properties of an axon that lead to a HIGH conduction velocity: A high membrane resistance – not many ion channels open – ability to resist charge A low membrane capacitance – if it can leak ions – ability to store charge. Myelination takes away the ability to store charge, lowers capacitance A large axon diameter which leads to a low cytoplasmic resistance Capacitance is the ability to store charge, a property of the lipid bilayer. A high capacitance takes more current to charge and can cause a decrease in the local current spread and thus a decreased conduction velocity. A low membrane resistance has many ion channels open and so also decreases local current spread. |
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Explain the local circuit theory of propagation
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injection of current into an axon will cause the resulting charge to spread along the axon and cause an immediate local change in the membrane potential. Local currents cause the action potential to propagate down the axon in one direction; they cannot go backwards because the area that has just fired an action potential is refractory
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Explain how conduction velocity is linked to fibre diameter.
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In myelinated axons – conduction velocity is proportional to fibre diameter. Max is 120ms-1.
In unmyelinated axons – conduction velocity is proportional to the square root of fibre diameter. Maximum velocity if 20ms-1 In small diameters, unmyelinated fibres conduct faster than myelinated fibres because there is a point where the axon is too small to wrap myelin sheath around. Myelinated fibres can’t be made as small as unmyelinated fibres can. Fibre diameter in myelinated fibres = axon + myelin sheath Fibre diameter in unmyelinated fibres = axon |
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Explain how myelination occurs and the implications of myelination for conduction.
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Myelination of axons is carried out by Schwann cells on peripheral axons and by oligodentrocytes in the CNS. The Schwann cells wrap their plasma membrane in many concentric layers around the axon.
Large diameter axons such as motorneurones are myelinated, whereas smaller ones such as C-fibres(sensory neurones) are not. Myelination increases conduction velocity by reducing the capacitance and increasing the resistance of the axon. Saltatory conduction occurs in myelinated fibres where the action potential jumps from one node of ranvier to the next which takes about 20ms. This occurs as the myelin sheath is an insulator of the intermodal region and so increases the resistance between the inside and outside of the cell (decreases open ion channels) and so inhibits charge leakage through the membrane. Therefore the charge can travel further without being lost, further than local spread. The nodes of ranvier have a very high density of sodium channels, where in unmyelinated fibres the sodium channels are spread out evenly. Myelinated fibres are more likely to have a larger diameter and so are easier to stimulate using stimulating electrodes. |
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Describe the consequences of demyelination
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Demyelination cause saltatory conduction to stop due to dissipation of local currents and increased capacitance of membrane.
After a few weeks, redistribution of ions occurs along the axon and the nerve begins to function as an unmyelinated nerve. Multiple sclerosis – disease of the immune system where the myelin is destroyed in certain areas of the CNS causing decreased conduction velocity and either complete block or cases where only some action potentials are transmitted Devic’s disease – optic and spinal cord nerves only. PNS: Landry-guillain-barre syndrome Charcot-Marie-Tooth disease |
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Can myelinated nerve fibres regenerate if cut from the central end?
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Yes in the peripheral nervous system, Schwann cells can re-myelinate axons.
Oligodendrocytes can’t and so doesn’t happen in the CNS. |
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What might be the effect of treating a demyelinated nerve fibre with an agent that blocks voltage-gated potassium channels?
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Blocking voltage gated potassium channels, prolongs the action potential as repolarisation is prevented. This allows the action potential to travel further and can restore nerve impulse conduction.
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Define saltatory conduction.
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Saltatory conduction occurs in myelinated nerves. Sodium and potassium channels only occur at the nodes of ranvier and so action potentials jump from node to node. The threshold potential must be reached at the nodes of ranvier. Myelin sheath insulates the intermodal axon and lowers capacitance and increases resistance so that charge can travel further without being lost.
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