Neurophysiology – lecture 19

March 24, 2011

1 Review:
1. Over the course of the last month we have been discussing the basis of action potential generation.
2. To summarize that material we have used two different models:
First, a positive feedback loop model showing
A small depolarization raising Vm above resting potential →
A rapid increase in m and a slower decrease in h and a slower increase in n →
An increase in gNa without much increase in gK →
An increase in inward INa without much change in IK →
A net inward ionic I →
An increase in intracellular + charge →
Added + charge to the membrane capacitor →
Further depolarization →
(Back to the start of this sequence)
Second, an Electrical Membrane Model whereby
An increase in gNa →
An increase in inward INa through the Na+ pathway and little change in outward IK through the
K+ pathway →
An increase in Inet flowing along the inside of the membrane →
Outward capacitive current →
Depolarization
The point is that these 2 models are describing the same processes in somewhat different terms, but
a student should be able to recognize a given process in one model and where an analogous process
occurs in the other model.
3. For the next topic – action potential propagation – it is important to remember and be able to apply
2 important concepts shown in the action potential generation lectures:
Threshold which is reached when the Inet is inward or, what is the same, when there is outward
capacitive current (which depolarizes).

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 Refractoriness which lasts for 5 to 30ms after an action potential and is due to:
(a) reduced INa due to reduced gNa due to a decrease in h
(b) a greater IK due to gK returning to resting level at a slow rate.
4. During the next few weeks we will be keeping and using these models but also adding components to
them to explain additional neural processes like action potential propagation, synaptic transmission,
etc.

2 Action potentials propagation along axons

1. So far we have been studying action potential generation in neuronal soma or in squid axons. In these
cases all the cell membrane is simultaneously experiencing the same transmembrane potential. That
is everything inside the membrane is said to be “isopotential” – i.e., at the same potential.
2. In neuronal soma that is true because these soma have a relatively large diameters and are filled with
a fairly good conducting medium – the cytoplasm – so that the resistance between one locus inside the
soma and another is quite small.
3. In voltage clamping the squid axon a wire was run down the center of the axon which kept the cytoplasm
along the length of the axon at the same voltage. Further, current recordings were only taken from
a small section in the center of that wire, so that those portions of axon on both sides of this center
section were experiencing the same voltage changes as the center section and therefore no current would
flow from the center section to these adjacent sections. This is referred to as a “space clamp.”
4. Looking at an Electrical Membrane Model of an axon as in Figure 13A (bottom) or, in a more complete
fashion, on the extra handout page, one sees that the axon can be diagramed as a sequence of sections
(A through E) where each section contains a Na+ , K+ , L and capacitive pathway – all the pathways
needed to produce an action potential. Thus, each section is capable of generating an action potential.
5. However, inside the axoplasm there is also a small resistor placed between each of the sections. Since
voltage differences can be produced across a resistor (Ohms Law), this resistor indicates that the
sections may not be at the same transmembrane potential. That is, the axoplasm is not necessarily
isopotential along the length of the axon.

3 Cable model
1. On the flip side of the handout showing a detailed model of an axon there is a model of a heavy
electrical cable. It is composed of a heavy copper wire surrounded by a good insulator and for the
purposes of this example it is a cable that was being considered to transmit electrical signals while
resting on the ocean bottom.
2. In a simple way this cable is analogous to an axon in having a good conductor in the inside, the
axoplasm, surrounded by an insulator, the membrane, and bathed in another good conductor – extra-
cellular fluid or seawater. Therefore, a cable might be used as a model for an axon.
3. This is relevant because in the mid 1800’s Queen Victorias government was trying to determine if it
would be possible to lay and then use a transatlantic cable to communicate with people in the western
hemisphere. They were smart enough to recognize that a potential disaster was in the making if they
laid 5000 miles of cable across the Atlantic only to find that a signal put into one end of the cable never
came out at the other end. So they wanted to do a “feasibility study” to determine if an electrical
signal could be carried across the bottom of the ocean and be received at the other end.

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 They offered a generous commission to anyone who could do the analysis successfully. The commission
was successfully completed by William Thompson, a Scot mathematician and scientist. You may not
have heard of William Thompson, but his name became familiar when some years later he was knighted
by the queen and given the name “Lord Kelvin.”
4. In the cable model that he used to derive the equations which answered the question of what was
needed to develop a successful transatlantic cable, you should note that there are 2 labeled resistors:
ri = longitudinal resistance of 1cm of cable and
rm = resistance of the insulation covering 1cm of cable.
These variables ri and rm can also be applied to the longitudinal and membrane resistance of a 1cm
length of axon. The units of ri are Ω/cm and the units of rm are Ωcm. Note: rm is not the resistance
of 1 cm2 of membrane.
5. The resulting second order differential equation does not have a general solution but can only be solved
for specific cases.
The equation is called the “Cable Equation” and is:

∂ 2 Vm ∂ Vm
λ2 −τ + Vm = 0
∂ x2 ∂t
r
rm
where τ = time constant and λ = length constant = (Don’t worry you don’t have to use this
ri
equation, just admire it.)
dVm
6. However, the equation can be solved in one simplifying case: when = 0, i.e., when the voltage
dt
across the cable or axon membrane is not changing.
dVm
= 0 when at the end of a long rectangular current pulse the change in transmembrane potential
dt
produced remains constant, i.e., a plateau in the transmembrane potential has been reached.
7. In this case the maximum change in transmembrane potential produced by the current pulse gets
smaller and smaller as the recording site is moved away from the site of current injection. The site of
current injection is therefore the site of the largest change in transmembrane potential anywhere along
the axon. In the diagram Figure 13B this voltage is labeled V0 .
The decay in transmembrane potential is exponential with distance and can be fitted with the equation
−x
Vm = V0 e λ . See Figure 13A middle diagram.
8. That this equation not only fitted cables but also fitted the data from axons was shown by Hodgkin
in 1937. He showed that a propagated action potential was preceded by a smaller depolarization thus
showing that currents and depolarization traveled out ahead of a propagated action potential and that
this depolarization was important in producing action potential propagation.
He also observed that this area of depolarization preceding an action potential decayed in an exponential
fashion as the recording site was moved farther away from the action potential. In this regard the axon
was behaving like a cable.
9. The membrane capacitance also affects the form of the depolarization as seen in Figure 13B. As the
recording site moves farther from the site of current injection the slower does the depolarization rise.
10. In Figure 13C both the effect of time after the current injection labeled t and of distance from the site
of current injection labeled x are shown. Obviously, the mathematics required to generate all these
curves is complex.

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4 Cable theory applied to axons
1. When cable theory is applied to axons we become aware of some sobering truths.
The length constant, λ, of the squid axon is about 6.5mm. This reflects the fact that 1)the axon
membrane is “leaky” and so has a relatively low resistance, rm , when compared to insulation on a wire
and 2) the axon is of small diameter and filled with only a moderately good conductor so ri is larger
than for a wire.
2. At a distance of 1λ from the site of current injection only 0.37 of the initial signal remains; at 2λ only
0.14 of the signal remains, at 3λ only 0.05 of the signal remains. Therefore, even for a squid axon a
100mV action potential would appear as only a 5mV depolarization at a distance of 19.5mm, i.e., less
than 2 cm!
3. This is not a good way to propagate information over a long distance.
4. However, action potential conduction velocity does depend heavily on λ as we shall we next time.