Neurophysiology – lecture 21

March 31, 2011

1 Review:
1. The spread of depolarization along an axon is insufficient to convey information any distance along the
axon since the length constant is so short (<1cm).
2. Qualitative model of A.P. propagation
A.P. generated at point A along the axon →
Spread of depolarization to point A+1 →
Depolarizes A+1 above threshold →
An A.P. arises at A+1 → (back to the first step, but at A+1)
Thus, A.P. propagation is really the sequential generation of new A.P.s in successive areas along the
axon with each new A.P. triggered by an A.P. in an adjoining axon segment.
These new A.P.s all look alike because they are produced by the same channels, from the same ions
with the same concentrations present in an axon of the same size. But they are individually generated
by different segments of axon.
3. Once initiated A.P.s can only travel in one direction because the locus at which they were just generated
has become refractory and cannot support another A.P. for a short period.
4. The form of the A.P. as distributed along the axon at a point in time is the same form as that of an
A.P. distributed in time and recorded at one point.
r
rm
5. The first depolarization at the onset of an A.P. rising to about 20mV is exponential; where λ =
ri
6. Large axons have longer ls since l is proportional to the square root of the axon radius.

2 How do myelinated axons conduct A.P.s?

1. First the structure of myelin as shown in Figure 14A was described. Myelin is formed by multiple layers
of glial membrane warped around an axon with all the cytoplasm between the layers of membrane
having been squeezed out.
2. Myelin with up to 275 layers of membrane has been observed.
3. The diameter of a myelinated axon is about 1.66 times the diameter of the axon itself.

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 4. At regular intervals along the myelinated axon there is a break in the layers of myelin called Nodes of
Ranvier. (See Figure 14B.) At a node there are no layers of glial membrane only the surface membrane
of the axon. (See Figure 14C.)
5. The internodal distance along a myelinated axon is on the order of 1mm, though larger diameter axons
have longer internodal distances.

3 Electrophysiology of myelinated axon A.P. propagation

1. If each layer of membrane in the myelin has a certain resistance to current passing through it (as all
membranes do), then the n layers of membrane composing the myelin sheath will have n times the
resistance to current passage and thus form a formidable barrier to the passage of current through
them.
2. The voltage difference produced across these layers of membrane by any current that does pass through
them will be greater than the voltage difference produced by that same current crossing the axon
membrane. If there are say 10 layers of membrane in the myelin and a 100mV is imposed between the
inside of the axon and the outside of the myelin, then one could expect that 10/11th of that voltage
difference will be across the myelin and only 1/11th will be across the axon membrane. However, at
the nodes where there is only the axonal membrane all of the 100mV will be imposed across the axonal
membrane.
3. Figure 14D shows an electrical model of a myelinated axon where the myelinated segments of the
axon are shown with a large resistance, rmyelin , shown in series with a smaller resistance, rmembrane ,
representing the axon membrane resistance.
In the graph of trans-axonal-membrane potential vs. position along the axon, it is shown that a large
depolarization applied to the left hand side of the axon will produce a large depolarization across the
axon membrane only at the nodes of Ranvier.
4. Of course any large depolarization, like an action potential, produced at one locus along the axon will
decay to a smaller value as the distance from the action potential generation site increases. (Shown by
the decaying slope of the potential recorded across the axon membrane portrayed in black.)
5. Only at the nodes will the axon transmembrane potential exceed values which we would except would
elicit a new action potential. Thus, new action potentials will be generated only at the nodes and not
in the myelinated areas the axon.
6. A second factor contributes to the fact that action potentials are produced only at nodes, namely there
is a considerable concentration of voltage-sensitive Na+ channels at the nodes (about 5000/mm2 ) and
very few such Na+ channels along that axonal membrane which is under the myelin. For comparison
the concentration of Na+ channels in a squid axon membrane is about 300/mm2 . Thus the only place
where there is the molecular machinery to produce action potentials is ar the nodes.
7. Tasaki in 1941 recorded currents flowing from 0.75 mm stretches of individual myelinated axons. As
seen in Figure 14E, if the 0.75mm stretch from which the recording was made (as shown by the Y-
shaped drawings on the right hand side of the figure positioned near a drawing of the myelinated
axon.)
If the 0.75mm stretch of axon included only a myelinated section of axon, there was almost no current
recorded.
If the 0.75mm stretch of axon included a node then a relatively large current was seen.

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 This provided a compelling demonstration that transmembrane currents and action potentials are
generated only at nodes along the axon.
8. How many nodes are simultaneously active during an A.P. propagated along a myelinated axon?
Because of Tasaki’s demonstration that action potentials occur only at nodes, writers began to describe
action potential propagation along axons as being “saltatory” thereby suggesting that action potentials
“jump” from node to node.
9. If an A.P. generated at a particular node had an insufficient spread of voltage along the axon to
depolarize the adjacent node above “threshold” then it would not be propagated anywhere.
10. Instead an A.P. generated along a myelinated axon depolarizes above threshold at least 4 nodes along
the axon ahead of it peak and an equal number along the axon length behind it. Thus, multiple nodes
are simultaneously involved in A.P. generation along a myelinated axon.

4 Comparison of myelinated and unmyelinated axons

1. There are many examples wherein the q of a large unmyelinated axon equals or exceeds the q of a
myelinated axon, so myelinated axons do not always produce the most rapid q.
2. If we assume that a myelinated axon is covered with 100 layers of glial membrane, we might expect
that that axons λ would increase by a factor of 10 over what it might be if the axon were unmyelinated.
r
100 rm
λmyelin = = 10λunmyelinated
ri
For an unmyelinated axon to increase its λ by a factor of 10 would require
r
Rm √
λunmyelinated = a
2 Ri
So the axon radius must increase by a factor of 100 to increase λ by a factor of 10.
But if the radius increases by a factor of 100 the volume occupied by the axon increases by a factor
10,000!
Which is to say that a 14mm myelinated axon would have a similar λ to a 1.4mm unmyelinated axon!
So your nervous system would have to expand greatly to produce conduction velocities with unmyeli-
nated axons that are equivalent to the conduction velocities presently produced with myelinated axons.
3. The layers of membrane in myelin also have capacitive properties. Capacitors in series (as the mem-
branes in myelin are in series) equal an equivalent capacitor equal to the capacitance of 1 membrane/the
number of membranes in the series. This is to point out that stacking membranes one on top of another
greatly reduces their equivalent capacitance. As shown in Figure 13B the larger the capacitance that
must be charged up before the transmembrane potential begins to increase due to current injection,
the slower is the change in transmembrane potential.
This factor slows down the spread of depolarization along unmyelined axons. But since the capacitance
of myelinated axonal membranes is much less than that of unmyelinated membranes, the spread of
depolarization along myelinated axonal membranes is relatively faster which contributes to a faster
A.P. conduction velocity.
4. Since inward Na+ current occurs only at the nodes of Ranvier rather than along the entire length of the
axon, there is less flux of Na+ into the axon than is the case for an unmyelinated axon. This provides
a considerable saving of energy (ATP) which might otherwise have to be used to pump this Na+ back
out of the cell by means of the Na+ –K+ exchange pump.