The propagation of action potentials along the axon.
Christiane – HOM2 1Depolarisation: Perturbation of the membrane potential towards a larger (i.e. more positive) value.How is an action potential propagated along the axon?An action potential is a short-lasting spike-like change in the membrane potential thatis passed along an axon as a result of a trigger/stimulus (Figure 1). The trigger can bea small change in charge distribution across a membrane caused by mechanically-gated ion channels responding to mechanical stress, or by the action ofneurotransmitters on ligand-gated ion channels. This initial depolarisation is sensedby a small amount of voltage-gated Na+ channels, causing them to open. Na+ ionscan now flow into the cell along their concentration gradient, changing the chargedistribution and hence causing an even bigger depolarisation of the membrane. This inturn results in more Na+ channels to open, increasing the Na+-permeability of thecell.If the initial stimulus is large enough and the chain-reaction of opening Na+ channelsaffecting their neighbours occurs quick enough, then a positive feedback-loop isinitiated, leading to a very fast increase in membrane potential (area 1 in figure 1).The permeability to Na+ becomes so large that the value of the overall potential in thearea where the action potential occurs almost reaches that of a cell solely permeableto Na+.As a result of the depolarisation of the membrane, voltage-gated K+ channels alsostart to open, but with a slight delay compared to the Na+ channels. Once opened, K+ions start to flow out of the cell along their concentration gradient, which is largerthan that of Na+ (K+ inside/outside = 20/1, Na+ inside/outside = 1/9). This is how theflux of K+ ions can quickly catch up with the Na+ flux. In fact, the Na+ flux is evenoutweighed by the K+ flux since Na+ channels start to close at this point. The closureof Na+ channels is purely time-dependent and once they are closed, Na+ channelsremain inactivated for 10ms even when the resting potential has been re-established.Hence, after the initial rise of the membrane potential towards the value of Na+, themembrane potential now moves quickly towards the value of K+, as a result of themembrane now being primarily permeable to K+ ions (see area 2. figure 1). As theclosure of the K+ channels is voltage-dependent, K+ channels start to close at this
Christiane – HOM2 2point and the membrane potential then returns back to its resting value, which still liesrelatively close to the potential of K+ alone (area 3. figure 1). Plot of the action potential E (Na+) 1. 2. 3. E (K+) Figure 1. Adapted from http://courses.cit.cornell.edu/bionb441/FinalProjects/f2006/sjj26/491_SJJ26/Action_Potential.JPGAn action potential only occurs in a limited area of the cell membrane, but thechanges in membrane potential at the edges of this area are enough to initiate anotheraction potential in a neighbouring space, which then gives rise to another actionpotential further down the axon and so forth. This is how action potentials arepropagated along the length of the axon. The inability of Na+ channels to re-openafter the first action potential was fired ensures that the wave of action potentialstravels only in one direction, that is away from the initial area of depolarisation.Passing on small perturbations of the membrane potential across larger distances in anaxon is difficult as the signal decays across the length of the membrane. This(exponential) decay is a result of leakage of the current transmitting the depolarisationalong the axon to the surrounding areas. The action potential is a good way to preventthis loss of signal along the axon as each individual action potential recovers thestrength of the original signal. As long as the threshold is overcome, it does not matterwhat the absolute size of the initial depolarisation was (all-or-nothing law), the actionpotential will occur to completion. In case of a failed initialisation without actionpotential (yellow line in figure 1), the signal decays along the length of the
Christiane – HOM2 3membrane, the cell eventually returns to its resting state. This is known as passive orelectrotonic potential. This way of signalling is not effective across large distancesand is therefore only employed by small neurones, some of which are located in theretina of the eye. The decay of the signal as a function of distance is described by thelength constant, which is the distance at which the voltage has decayed toapproximally 1/3 of the initial value. If the distance across which the signal needs tobe transmitted lies below the length constant, then passive transport is appropriate. Ifthe distance is larger, then active transport using action potentials is required.Nice movie of propagation of action potentials in myelinated and unmyelinatednerves: http://www.blackwellpublishing.com/matthews/actionp.html
Christiane – HOM2 4What factors affect the velocity of conduction?The speed with which a signal is transmitted along an axon is quite important, as thequick response to a stimulus may decide over life and death of an animal exposed to athreat. This is why several ways to accelerate nerve impulse conduction have beendeveloped throughout evolution:One way to increase the speed of conduction is through insulation of nerve fibres bymyelination. Myelin sheaths are areas in which the cell membrane of nerve-supporting glial cells (Schwann cells in peripheral nerves or oligodendrytes in theCNS) is wrapped around the axons. This enlarges the thickness of the nerve fibrewall, and thereby increases the electrical (transverse) resistance across themembrane (Resistance increases as a wire becomes longer). Charges can thereforemore easily flow longitudinally, which is the desired direction. Furthermore, areas ofmyelination don’t contain Na+ channels, which further increases the transverseresistance, ensuring that even more ions causing depolarisation can flowlongitudinally along the axon.Myelination also reduces the capacitance of the membrane, as this is inverselyproportional to the thickness of the insulating layer in a circuit. Since capacitance isdefined as charge over voltage, a lower capacitance for a set number of charges oneach side of the membrane results in a larger potential difference established.The combination of these two effects increase the speed with which potentialdifferences are passed along the axon, as well as the range with which an actionpotential can affect neighbouring areas. Assuming that currents passing in thelongitudinal direction move faster than voltage-induced membrane channels open(requires protein rearrangements which happen on a slower timescale than ions movein solution), it is probably in the interest of speed to fire fewer action potentials andextend the range of passive propagation of currents.The myelinated areas are interrupted by so-called “Nodes of Ranvier”, small stretchesof uninsolated axon with a high concentration of Na+ channels. When adepolarisation current reaches a Node of Ranvier, a new action potential is generatedwhich is then quickly passed through the next area of myelin insulation to theadjacent Node of Ranvier. This is called saltatory (“jumping”) conduction andprovides an excellent way to speed up the propagation of the action potential while
Christiane – HOM2 5conserving metabolic energy: Using too many Na+ channels would require a lot ofATP to pump the Na+ back out of the cell against its concentration gradient.Another way in which faster neuronal communication has evolved is throughenlargement of the axon diameter, i.e. the interior compartment containing theaxoplasm. This is also called “axonal gigantism”. Just like in a metal cable thatconducts electricity, a wire with a larger diameter results in a drop in longitudinalresistance, which ensures that the depolarisation can be passed on more efficiently.In summary, the following parameters affect the speed of conduction: 1. Leakage of ions: decreases the longitudinal flow of current and is linked to the resistance of the cell membrane as well as its capacitance. This is compensated by myelination. 2. The thickness of the membrane: affects its resistance and its capacitance. This is again optimised by myelination. 3. The inside diameter of the axon containing the axoplasm: This affects the longitudinal resistance and can be optimised by axon gigantism. Extracellular matrix R↑↓ needs to be large C↑↓ needs to be small Myelin layers Axon membrane Na+ channels Q Longitudinal flow of charges needs to be optimised for signal propagation. R↔ needs to be small Q, I ↔ needs to be large Axoplasm = intracellular matrix
Christiane – HOM2 6Useful plot: Diameter of diameter versus conduction velocity achieved Myelinated = linear velocity Non-myelinated velocity higher for a diameter unmyelinated below 1um! V ~ √diameter For diameters larger than 1um, myelination increases the speed of conduction! 1µm diameter (myelination!!!)in organisms with myelin: - if diameter > 1um myelinated - if diameter < 1um unmyelinated - some exceptions in the brain where neuron density is so high (protect from extracellular environment)