Faculty of Health
Department of Community Health and Social Work
Learning Disability Division
Neurophysiology Workbook
Fiona Rich
Senior Lecturer
Focal Epileptogenesis
Nerve cells or neurones are specialised for receiving and transmitting electrical
signals. Neurones can be considered to have 3 zones – see figure 1:
Nerve Cell
1. Receiving Zone – impulses are received
by the dendrites which can be contacted
by other nerve cells at junctions known
as synapses
2. Conducting zone – signals pass down
the conducting part of the cell, the Axon
Nodes of Ranvier
3. Output Zone – The signal reaches the
nerve terminals (via the Axon) which
make synaptic contact with other cells
Figure 1
Membrane Potential
It is known that a cell has a small voltage
difference across its membrane. This can be
detected by the use of a volt-meter by placing one
electrode inside the cell and one outside. The
voltage – or potential difference is very small
(between 5 and 100mV) and shows the inside of
the cell as having a net negative charge and the
outside having a net positive charge.
This potential shows large changes between rest
(the resting potential) and activity (the action
potential) which is due to a sequence of
permeability changes to Sodium and Potassium
within the cell.
Figure 2
Resting Potential
It is also known that the fluid inside the cell (the
intracellular fluid) has a high concentration of
potassium ions (K+) and a low concentration of
sodium ions (Na+) which is the opposite in extra
cellular fluid (the fluid outside of the cell) i.e. it has a
low concentration of K+ and a high concentration of
Na+.
K+
K+
K+
Na+
Na+
Figure 3
The presence of the Active Transport system within the cell membrane acts as a
carrier to transport K+ into the cell and Na+ out of the cell – this is known as the
Sodium-Potassium Pump.
Potassium ions diffuse out of the cell down their concentration gradient, but the buildup of a positive charge outside of the membrane repels the movement. The
movement of ions is also repelled by the NaK pump.
If the cell membrane was permeable only to K+, potassium ions would diffuse out of
the cell carrying a positive charge. These positive charges would cause a small
potential to build up across the membrane until the electric force was big enough to
cause a flow of K+ back into the cell equal to the flow of K+ down the concentration
gradient. This is known as the equilibrium for potassium.
The activity of the NaK pump and the positive charge contributes towards the resting
potential. The resting potential therefore (which is between -70 and -90 millivolts
(mV)) represents the point at which there is no net movement of ions such as
potassium or sodium ions.
Action Potential
At rest, there is a continual slow leak of K+ out of the cell and Na+ into the cell. If the
membrane is stimulated (e.g. a chemical, mechanical or electrical stimulus) the
stimulus will increase the membrane's permeability to sodium. Sodium ions are now
entering the cell faster than potassium ions are leaving, which reduces the negative
charge enough to first depolarise the membrane potential (neutralise the charge) and
then to alter the negative charge to a positive charge (see figure 4).
The peak of the action potential is reached as the charge increases to +30mV, the
plateau is maintained for a fraction of a millisecond then the permeability to Na+ is
suddenly reduced as the effect of the stimulus wears off.
The membrane's permeability to K+ then increases, the downward phase of the
action potential is caused by the loss of potassium ions which diffuse down the
concentration gradient. This reduces the electrical charge (repoloarisation) so that
the potential returns to its resting charge of -70mV. At this point, the membrane
potential actually becomes more negative than the resting potential of -70mV (hyperpolarisation). This is due to the membrane's permeability to K+ remaining higher
than normal. To restore the status quo, the sodium-potassium pump is stimulated by
the increase of Na+. This removes the Excess Na+ and restores the lost K+.
Figure 4
Hyper-polarisation stage
(after potential)
Refractory Periods
A neurone cannot be re-stimulated if already firing, but may be re-stimulated during
the “after potential” (hyper-polarisation stage). However, the strength of the stimulus
will need to be stronger if the threshold is to be reached, as the membrane potential
is further away from the Threshold Potential during this phase.
Threshold Potential
Each neurone has a threshold potential which is 5 to 15 mV less negative than the
resting potential. If a mild stimulus is applied to a neurone, this can result in
depolarisation. This mild stimulus may not be strong enough to allow the membrane
potential to reach its threshold and will therefore not follow on to an action potential.
(You can see figure 4 above, a number of failed initiations at the point of the
stimulus.) An action potential will only follow if the stimulus is strong enough to take
the Na+ up to the Threshold point or beyond.
A stimulus not strong enough to reach Threshold Potential is known as a Graded
Potential – it is not a fixed size.
If the stimulus is strong enough to reach the threshold point, an action potential will
follow, but the size of the action potential will not change. This is known as the ‘all or
none’ principle.
Spread of Action Potentials
In unmyelinated fibres, the action potential is transmitted along the neurone by local
current flow: the active part of the cell has reversed charges to the resting part. The
positive ions inside the active part of the cell are attracted to the adjacent resting
section which is negative. The negative charge starts to depolarise to threshold
value where an Action Potential is set up. This is known as a positive feedback
system.
Depolarisation
Axon
+++ --- +++
- - - + + + - - - +++
Positive ions are attracted to negative
ions, the negative charge depolarises
and an action potential is set up
Repolarisation
Depolarisation
Axon
- - - + + + - - - +++
+++ ---+++
Figure 5
As an analogy, imagine a crowd of people doing the Mexican Wave, or a row of trees
catching fire where the wind blows the flames from one tree to the next:
Figure 6
Large axons are covered with myelin which consists of a wrapping of many layers of
cell membrane interrupted every few millimetres by the gaps of the Nodes of Ranvier.
This myelin sheath insulates the axon so charges cannot diffuse. Action potentials
therefore can only be set up at the nodes of Ranvier where there are gaps in the
sheath (see figure 1). This is known as saltatory (jumping) conduction.
Synapses
The junctions between neurones (the synapses) can be divided up into 2 types –
electrical and chemical. However, the majority of synapses in the human brain are
chemical.
Chemical Synaptic Transmission
At chemical synapses, there is a cleft between pre- and postsynaptic cell. In order to
propagate a signal, a chemical transmitter (e.g. glutamate) is released at the
presynaptic terminal. This release process is called exocytosis. The transmitter
substance diffuses across the synaptic cleft and binds to receptors at the
postsynaptic membrane, thus opening an ion channel. Chemical transmission is
slower than electric transmission.
For this to happen, the axon branches out into non-myelinated fibres, at the end of
which is a structure known as a bouton – the pre-synaptic terminal. The pre-synaptic
terminals contain mitochondria, micro filaments, smooth endoplasmic reticulum and
vesicles which lie close to the membrane.
When a nerve impulse arrives at the bouton, it causes an influx of calcium ions
(Ca2+) which trigger the release of transmitter substances into the synaptic cleft. For
this to occur, some vesicles fuse with the membrane and release their contents
before releasing themselves from the cell wall ready to be refilled with transmitter
substance in a recycling process.
Figure 7
The chemical transmitter substance diffuses across the synaptic cleft to the post
synaptic membrane where it interacts with receptor molecules to bring about an
immediate change in the permeability characteristics of the post-synaptic neuronal
membrane, which leads to excitation or inhibition of the neuron, depending on its
receptor characteristics.
Excitatory Synapses
The neurotransmitter-receptor combination causes an increase in the permeability to
cations such as Na+ causing the electrical charge to depolarise. The difference in
voltage between the resting and depolarised levels is known as the excitatory post
synaptic potential (EPSP) and is a type of graded potential. (See figure 8)
Inhibitory Synapses
In this case, the neurotransmitter-receptor combination reduces transmission
between neurones as the post synaptic cell membrane becomes hyper polarised and
therefore refractory to stimulation. This may be due to an efflux of positive charge
out of the cell (e.g. potassium) or due to an influx of negative charge into the cell,
such as chloride ions (Cl-). The difference in voltage between the resting and hyper
polarised potentials is known as the inhibitory post synaptic potential (IPSP).
Figure 8
Neurotransmitters
Only a few transmitter substances have been identified with certainty – these can be
said to have excitatory and/or inhibitory properties:








Acetylcholine
Noradrenaline
5-Hydroxytryptamine
Glutamic Acids
Asparic Acids
Gamma-Amino-Butyric Acid (GABA)
Glycine
Dopamine
Integration of Synapses
In most instances, a single EPSP is insufficient to generate an Action Potential. In
order to produce a post synaptic impulse, several EPSP's must summate to produce
excitation. This may result either from the summation of many successive EPSP's
produced by activity in a single pre-synaptic neurone – i.e. temporal summation, or
from the summation produced by activation of different pre synaptic neurones known
as spatial summation.
The chemical transmitter substances have a short-lived action which is necessary for
precise control. The transmitter substances may be destroyed by enzymes in the
synapse as with Acetylcholine: The enzyme cholinesterase – present in the post
synaptic cell membrane – splits the molecule into Acetate and Choline. Choline can
then be transported back into the nerve terminal and re-utilised by the cell.
Electric Synaptic Transmission
The nerve impulse travels along the axon by means of local current flow as described
above. If the membranes of the pre and post synaptic cells are close together and
the cleft between them is small, the current can flow from one to another to produce
excitation
At electrical synapses, the current generated by the action potential at the
presynaptic neuron flows directly into the postsynaptic cell, which is physically
connected to the presynaptic terminal by a so-called gap junction. However, if there
is no physical connection between the two cells is large, the current will flow into the
intercellular space and there will be no direct flow of current into the post synaptic
cell. In this case, excitation must be assisted by a chemical transmitter substance.
Epilepsy
The diagnosis of epilepsy can in part be supported by evidence of neuronal activity
detected via an electroencephalograph (EEG). The surface EEG represents the
summation of millions of neuronal potentials. Surface ‘spikes’ on the EEG are related
to an increase in the number of neurones firing and represents a summation of
EPSP’s. Slow ‘waves’ on the EEG are related to a reduction in neuronal firing and
represents the summation of IPSP’s. This is why on an EEG of a person with
epilepsy (see figure 9); you will see a large number of spikes, demonstrating
excessive electrical activity.
Ictal Activity
Figure 9
Where ictal EEG activity is recorded (i.e. when a seizure is taking place) this
represents the summation of continuous changes in the membrane’s permeability to
Na+ which causes depolarisation (known as the paroxysmal depolarising shift). In
other words the brain is experiencing excessive EPSP’s – this excessive electrical
activity builds up causing uncontrolled stimulation of the brain. Excitatory cells fire in
rhythmic, uncontrolled bursts which can spread from a localised area of the brain to a
generalised area, eventually involving the whole brain.
Normally, there is a relatively low level of electrical activity in the brain. In those who
have epilepsy, it is known that there is a loss of inhibitory cells and that there is an
inability to switch off cells once they have been stimulated – there is nothing to stop
cells from firing.
The clinical accounts of seizures often reflect the spread of seizure activity. There is
evidence that seizures spread through a ‘preferred’ pathway, and that this take place
along myelinated pathways. However, seizures may also spread through local
current flow as described earlier. You will be examining the effects of the spread of
electrical activity in further workbooks.
On the following page, you will find a series of questions. You will find the answers to
these in the pack but you are strongly advised to supplement your reading with
physiological and neurophysiological text books.
Please answer these questions and e-mail your answers to
[email protected]
1. In your own words, explain what is meant by a membrane potential
2. In your own words, explain the events that occur during the
depolarisation and repolarisation stages of the action potential
3. In your own words, explain what is meant by the threshold for initiation
of the action potential
4. In your own words, explain what EPSPs and an IPSPs are
5. Find examples of a chemical, mechanical and electrical stimulus that
may elicit an action potential.
6. In your own words, explain what is meant by the ‘all or nothing principle’
7. Explain the difference between temporal and spatial summation
8. Briefly and in your own words, explain neurologically what is happening
during a seizure