Session 4 Flashcards
Which two ions does the action potential in axons depend upon?
Na+ and K+
What happens when sodium channels in an axon membrane open?
The sodium concentration will change in order to try and reach the sodium equilibrium potential; as ENa is positive, this causes depolarisation of the axon
What effect does reducing extracellular sodium concentration have on the action potential?
Reducing extracellular sodium reduces ENa, and hence reduces the upstroke of the action potential
What prevents sodium channels in an axon membrane from reaching ENa?
The opening of potassium channels (repolarises the axon)
What is the conductance of a membrane of any ion dependent on?
The number of channels for the ion that are open
What effect will conductance have on an ion for which the equilibrium potential is the same as the membrane potential?
There will be no effect
For an axon with diameter 1um and resting [Na+] of 10mM, what percentage change of Na+ is needed to bring about the action potential?
0.4% - action potentials do not represent a reversal in gradients, they are just small changes in ionic concentrations
How does voltage clamping enable the measurement of ionic currents?
A second electrode is inserted in the membrane, enabling the membrane voltage to be controlled; this enables the flow of ions to be observed at certain voltages
What happens when the membrane is depolarised by a voltage clamp?
What happens if the voltage is increased (becomes more depolarised)?
There is an influx of sodium (voltage gated channels) which will eventually stop, and there is a longer lasting outflow of potassium ions; the changes occur more rapidly
What happens when the membrane has been depolarised to ‘threshold’?
Once triggered, voltage gated Na+ channels open and Na+ enters the cell, depolarising it; this causes the depolarisation of more voltage gated sodium channels (positive feedback)
What is the ‘all or nothing’ principle?
For an action potential (depolarisation) to occur, a certain level of depolarisation must be met in order to activate the positive feedback of Na+ channels opening; if the threshold is not met, then the positive feedback cannot occur, and there will be no action potential
What happens during the ‘downstroke’ of the action potential?
Na+ channels become inactivated (they are susceptible as soon as they are open), and Na+ influx stops. Simultaneously, the depolarisation causes the opening of voltage sensitive K+ channels, and the influx of K+ into the axon causes repolarisation (they aim for the K+ equilibrium potential)
What is the ‘absolute refractory period’?
A period within which another action potential cannot be generated, enabling the propagation of action potentials in a single direction only; it occurs due to the properties of Na+ channels (inactivated state)
What is the ‘relative refractory period’?
A period within which another action potential can be generated, but a greater stimulus is needed due to the hyperpolarisation of the membrane; it occurs due to the properties of Na+ channels (returning to closed state)
What is the principle of ‘accommodation’?
The longer the stimulus (without reaching threshold), the greater the intensity of the stimulus needed to initiate depolarisation
Why does an increase in length of stimulus cause a decrease in size of depolarisation?
When the stimulus begins, Na+ channels become inactivated (fewer in closed state); the longer the stimulus, the more channels that are already inactivated when threshold is met and hence the lower the number that are open during the depolarisation (lower conductance) = smaller action potential
Describe the basic structure of a voltage gated sodium channel
4 repeats (same protein) of the same 6 transmembrane domain units; they fold around to create a pore
What is special about transmembrane section 4 (‘S4’) of each of the four repeats in a voltage gated sodium channel?
It has many positively charged amino acids, and is known as the ‘voltage sensor’; a change in voltage across the membrane will cause a conformational change in this section, allowing the opening of the pore and hence the flow of sodium
What is found between subunits III and IV of the voltage gated sodium channel (‘H5’)?
This is a section called the inactivation particle; when the channel is open, it can enter the pore and block it, stopping the flow of sodium through the channel and rendering the channel ‘inactivated’
Describe the basic structure of a voltage gated potassium channel
4 separate subunits, each with 6 transmembrane domains; they have an ‘S4’ voltage sensor region, and a ‘P’ (or H5) region which acts as a cell activity filter – it enables the distinguishing of Na+ and K+ ions (not completely selective)
How do local anaesthetics such as procaine act?
Procaine has two methods of action to block Na+ channels and hence stop pain fibres.
What is the hydrophobic pathway method of action of procaine?
No use-dependence; the procaine gets into the membrane and passes into the VG Na+ channel through the membrane, blocking the pore
What is the hydrophilic pathway method of action of procaine?
Use-dependent; the procaine crosses the membrane, and reacts with H+ inside the cell – when the VG Na+ channel is activated and open, it enters the pore and blocks it
What determines the relative importances of the hydrophobic and hydrophilic methods of action of Na+ channel blocking anaesthetics?
The lipid solubility of the drug
In what order do local anaesthetics block axons?
Small myelinated axons, unmyelinated axons, and lastly large myelinated axons
How are action potentials recorded? (in squid axon)
Use of a pair of extracellular electrodes which induce a change in membrane potential; recording can be monophasic or diphasic depending on the location of the voltmeter (whether there is a damaged section of axon)
Why are there multiple action potential peaks when recording action potentials? (in squid axons)
There are differently sized axons within the nerve fibre
What is the ‘electrotonic potential’?
Injection of charge at a particular point in the axon will result in an immediate repelling of other charges in both directions as it spreads
Why does the change in membrane potential decrease further away from the injection of current?
Charge leaks out of the axon
What is the length constant?
The distance it takes for the relative membrane potential to fall to 37% of its original charge after injection in the membrane; the further the spread, the faster the conduction velocity of the axon
What does membrane resistance depend upon?
The number of ion channels open; the lower the resistance, the more channels are open
What is the capacitance of the membrane?
The ability to store charge; this is a property of the lipid bilayer
How does increasing the capacitance affect the rate of voltage change?
The rate of voltage change is slower
How does increasing membrane resistance affect the length constant?
An increase in membrane resistance increases the length constant; hence, with fewer ion channels open, the length constant increases
What affect does membrane resistance have on conduction velocity?
V=IR; the higher the resistance, the higher the potential difference across it; more voltage means more voltage gated Na+ channels are open, making it easier to reach the threshold required to fire an action potential; a higher resistance increases conduction velocity
How does axon diameter affect conduction velocity?
I = V/R; the lower the resistance (in this case cytoplasmic resistance from a large diameter), the larger the current, therefore the action potential will travel further; the wider the diameter, the faster the conduction velocity
How does capacitance affect conduction velocity?
Capacitance is the ability to store; a membrane with a high capacitance will take more current to charge (or a longer time with a given current). Hence, the higher the capacitance, the slower the conduction velocity
What is the myelin sheath?
Repeated layers of plasmalemma wrapped around the axon, formed by oligodendrocytes in the CNS and Schwann cells in the PNS
Describe the distribution of Na+ channels along the plasma membrane
Very high density at Nodes of Ranvier (gaps in myelin sheath), light even distribution between nodes
What ratio of axon diameter to whole neuron diameter gives the optimum conduction velocity?
0.7 (e.g. 7um of axon with 3um of myelin)
What is the purpose of the myelin sheath?
Acts as a good insulator, allowing a greater distance of possible depolarisation (increased length constant)
How does the myelin sheath improve conduction in axon neurons?
Increases membrane resistance (more channels open due to higher voltage), decrease in capacitance; these increase the length constant, with a slight decrease in the time constant
Why is the decrease in time constant caused by myelin not problematic?
Conduction velocity is proportional to the length constant over the time constant; the massive increase in length constant allows inducement of an action potential over large distances (between nodes of Ranvier), and this allows rapid speed of conduction (salutatory conduction)
What effect will damaged myelin have on the length constant?
It will decrease; the next node of Ranvier may be too far to induce depolarisation in, and hence the action potential will no longer occur by salutatory conduction
What is Multiple Sclerosis?
Autoimmune disease that attacks myelin proteins, there can also be damage to the axon; all CNS nerves can be affected and hence the symptoms are variable
