1st year medical school physiology essay: How is an action potential propagated along the axon? What factors affect the velocity of conduction?

1. Christiane – HOM2 1
Depolarisation: 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 that
is passed along an axon as a result of a trigger/stimulus (Figure 1). The trigger can be
a small change in charge distribution across a membrane caused by mechanically-
gated ion channels responding to mechanical stress, or by the action of
neurotransmitters on ligand-gated ion channels. This initial depolarisation is sensed
by a small amount of voltage-gated Na+ channels, causing them to open. Na+ ions
can now flow into the cell along their concentration gradient, changing the charge
distribution and hence causing an even bigger depolarisation of the membrane. This in
turn results in more Na+ channels to open, increasing the Na+-permeability of the
cell.
If the initial stimulus is large enough and the chain-reaction of opening Na+ channels
affecting their neighbours occurs quick enough, then a positive feedback-loop is
initiated, 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 the
area where the action potential occurs almost reaches that of a cell solely permeable
to Na+.
As a result of the depolarisation of the membrane, voltage-gated K+ channels also
start 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 larger
than that of Na+ (K+ inside/outside = 20/1, Na+ inside/outside = 1/9). This is how the
flux of K+ ions can quickly catch up with the Na+ flux. In fact, the Na+ flux is even
outweighed by the K+ flux since Na+ channels start to close at this point. The closure
of Na+ channels is purely time-dependent and once they are closed, Na+ channels
remain 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+, the
membrane potential now moves quickly towards the value of K+, as a result of the
membrane now being primarily permeable to K+ ions (see area 2. figure 1). As the
closure of the K+ channels is voltage-dependent, K+ channels start to close at this

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point and the membrane potential then returns back to its resting value, which still lies
relatively 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.JPG
An action potential only occurs in a limited area of the cell membrane, but the
changes in membrane potential at the edges of this area are enough to initiate another
action potential in a neighbouring space, which then gives rise to another action
potential further down the axon and so forth. This is how action potentials are
propagated along the length of the axon. The inability of Na+ channels to re-open
after the first action potential was fired ensures that the wave of action potentials
travels 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 an
axon 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 depolarisation
along the axon to the surrounding areas. The action potential is a good way to prevent
this loss of signal along the axon as each individual action potential recovers the
strength of the original signal. As long as the threshold is overcome, it does not matter
what the absolute size of the initial depolarisation was (all-or-nothing law), the action
potential will occur to completion. In case of a failed initialisation without action
potential (yellow line in figure 1), the signal decays along the length of the

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membrane, the cell eventually returns to its resting state. This is known as passive or
electrotonic potential. This way of signalling is not effective across large distances
and is therefore only employed by small neurones, some of which are located in the
retina of the eye. The decay of the signal as a function of distance is described by the
length constant, which is the distance at which the voltage has decayed to
approximally 1/3 of the initial value. If the distance across which the signal needs to
be transmitted lies below the length constant, then passive transport is appropriate. If
the distance is larger, then active transport using action potentials is required.
Nice movie of propagation of action potentials in myelinated and unmyelinated
nerves: http://www.blackwellpublishing.com/matthews/actionp.html

4. Christiane – HOM2 4
What factors affect the velocity of conduction?
The speed with which a signal is transmitted along an axon is quite important, as the
quick response to a stimulus may decide over life and death of an animal exposed to a
threat. This is why several ways to accelerate nerve impulse conduction have been
developed throughout evolution:
One way to increase the speed of conduction is through insulation of nerve fibres by
myelination. Myelin sheaths are areas in which the cell membrane of nerve-
supporting glial cells (Schwann cells in peripheral nerves or oligodendrytes in the
CNS) is wrapped around the axons. This enlarges the thickness of the nerve fibre
wall, and thereby increases the electrical (transverse) resistance across the
membrane (Resistance increases as a wire becomes longer). Charges can therefore
more easily flow longitudinally, which is the desired direction. Furthermore, areas of
myelination don’t contain Na+ channels, which further increases the transverse
resistance, ensuring that even more ions causing depolarisation can flow
longitudinally along the axon.
Myelination also reduces the capacitance of the membrane, as this is inversely
proportional to the thickness of the insulating layer in a circuit. Since capacitance is
defined as charge over voltage, a lower capacitance for a set number of charges on
each side of the membrane results in a larger potential difference established.
The combination of these two effects increase the speed with which potential
differences are passed along the axon, as well as the range with which an action
potential can affect neighbouring areas. Assuming that currents passing in the
longitudinal direction move faster than voltage-induced membrane channels open
(requires protein rearrangements which happen on a slower timescale than ions move
in solution), it is probably in the interest of speed to fire fewer action potentials and
extend the range of passive propagation of currents.
The myelinated areas are interrupted by so-called “Nodes of Ranvier”, small stretches
of uninsolated axon with a high concentration of Na+ channels. When a
depolarisation current reaches a Node of Ranvier, a new action potential is generated
which is then quickly passed through the next area of myelin insulation to the
adjacent Node of Ranvier. This is called saltatory (“jumping”) conduction and
provides an excellent way to speed up the propagation of the action potential while

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conserving metabolic energy: Using too many Na+ channels would require a lot of
ATP to pump the Na+ back out of the cell against its concentration gradient.
Another way in which faster neuronal communication has evolved is through
enlargement of the axon diameter, i.e. the interior compartment containing the
axoplasm. This is also called “axonal gigantism”. Just like in a metal cable that
conducts electricity, a wire with a larger diameter results in a drop in longitudinal
resistance, 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

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Useful 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)