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402 Part 5 Central nervous system
P5.1 Introduction
Suppose you were to overhear two doctors discussing the neurobiology of
schizophrenia or enumerating the theories which seek to explain drug addiction. You
might well find it difficult to follow the thread of their conversation. But when you have
worked through this part of the book you will have acquired a knowledge of
neuropharmacology that would enable you to understand—even to take part in—
discussions of such complex topics.
Neuropharmacology is the study of the action of drugs on the nervous system. It involves
investigating the mechanisms by which drugs alter the function of the brain. A key goal is
to use this information to develop new medications, with improved efficacy and safety, for
diseases affecting the central nervous system. Drugs are also used as tools in order to
further our understanding of the way the brain works. Thus much of what we already
know about the brain, including how individual neurons work and how they communicate
with one another, has come from studies using drugs as tools.
We begin with a basic question: how does the brain work?
1) The brain consists of a neuronal network. Neurons connect to and communicate
with each other, forming a complex network. This is mainly done by the activation of a
neuron and the release of a neurotransmitter, which then reaches a synapse and
changes the activity of another cell.
2) Each synapse is a little computer. When neurons form synaptic contacts with other
cells (and in the brain they may form and receive many thousands) these contacts are
not like two wires meeting in an electrical circuit: thus each point of contact receives
both excitatory and inhibitory influences, both pre-synaptic and post-synaptic, all of
which determine the functional output from the synapse.
3) The neuronal activity is kept alive by the accelerator in the brain. Glutamate is the main
excitatory neurotransmitter in the brain. Most brain neurons are stimulated by
glutamate, which can be viewed as the accelerator pedal of the brain.
4) Neuronal activity is controlled and dampened down by a brake in the brain;
-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain.
5) Hundreds of other neurotransmitters also act on the neurons, refining and directing
neuronal activity. Some are capable of stimulating on their own, but mostly they
modulate and change the neuronal activity triggered by the action of glutamate within
neuronal networks.
So glutamate pushes neuronal activity up, GABA pushes it down, and hundreds of other
events occur at the same time. Can we translate this into useful information for
understanding treatment of disease in the brain? We can make a start: in epilepsy waves
of excitation pass, out of control, through neural networks; the glutamate activity
dominates over weak opposition from GABA. Put simply, GABA is too weak, so we want
drugs that increase the GABA influence; this is exactly what we have in the treatment of
epilepsy, as explained in Chapter 16. Also in that chapter the account of glutamate and
GABA as accelerator and brake, respectively, is developed in Box 16.1.
So we have immediately got a grasp of brain function in a way that enables us to
understand an element of drug therapy. To develop this further we need to look at the
different cell types of the brain, and their basic biology.
P5.4 Organization of the brain into regions 403
P5.2 The brain is mostly glial cells, not neurons
Before we move on to that, let’s think about one curious aspect of brain function. We talk
about neurons, how they project and interact, receiving and sending signals to each other
in a complex neuronal network that forms the basis for our thoughts and feelings, and
determines who we are. The brain is one of the largest organs of the body, with an
average weight of 1.3 kg. The adult brain contains approximately 100 billion neurons. So
is the brain mainly made up of neurons? Well, the answer is no. Neurons are outnumbered
at least 10-fold by glial cells (>1000 billion). These are conventionally thought of as a sort
of housekeeping system, ensuring that neurons are supplied with nutrients and oxygen,
keeping them healthy so that they can do their complex job. There are several types of
glial cells, the most abundant being astrocytes, followed by oligodendroglial cells. There is
no doubt that glial cells support neuronal activity, but they also play a role in
neurotransmission. For example, astrocytes are involved in the removal (taking up and
destroying) of some of the neurotransmitters, thereby terminating their action. But despite
the important functions of glial cells, the story of ‘drugs and the brain’ is still, as far as we
know, mainly about neurons and the mystery of their chemistry and networks.
P5.3 The biology of the neuron
There are fundamental aspects that are the same for all neurons, whether they are part of
the central or peripheral nervous systems. Most important for us here are:
1) excitation of the neuron by neurotransmitter (e.g. glutamate) receptors on the cell body
setting up the action potential, and its modulation by other neurotransmitters
2) the role of fast Na+ channels in the passage of the action potential along the axon,
leading to depolarization of the nerve terminal
3) the role of depolarization-sensitive Ca2+ channels at the nerve terminal in allowing Ca2+
into the terminal
4) the Ca2+-dependent release of neurotransmitters stored in vesicles into the synaptic
cleft, and modulation of this release by stimulation of receptors at the nerve terminal
(pre-synaptic receptors)
5) the stimulation by the released neurotransmitter of receptors on the innervated cells
(post-synaptic receptors)
6) removal of released neurotransmitter by breakdown (enzymes) or active uptake,
sucking the neurotransmitter back into the nerve terminal or into neighbouring cells.
Each of these stages is modified by drugs used to treat the brain disorders that are
described in the following chapters. Of course there is a vast amount of additional
information about brain neurons and their circuits that could be discussed, but to
understand what follows it is perhaps more useful to introduce some brain regions that are
encountered in this section of the book.
P5.4 Organization of the brain into regions
Brain anatomy can become shrouded in a confusion of terminology derived from the
names of long-dead anatomists, or their whimsical imaginings when looking at parts of the
brain. This is mixed in with overlapping, often obsolete, conceptions of connections and
404 Part 5 Central nervous system
A.
B.
Parietal
lobe
Frontal
lobe
Occipital
lobe
Figure P5.1 The human brain.
The external surface of the brain labelled with
the major divisions of the cortex.
Temporal
lobe
systems. But don’t be put off. Here, we introduce in a simple way some of the parts of the
brain which are mentioned later in this section.
When you look at the human brain you see the cortex, which literally means the outer
layer. This is divided into four main separate regions: frontal lobe, parietal lobe, temporal
lobe, and occipital lobe, as shown in Figure P5.1. The cortex forms deep convolutions
over the surface of the brain (see Figure P5.2A). If we were to take a fresh brain and push
the cortex apart and to one side (this is easily done—it is very soft), we would see below
clearly visible regions. These are the subcortical regions, and some are shown
diagrammatically in Figure P5.2B.
Hippocampus
Nucleus
accumbens
Amygdala
Cortex
Hypothalamus
Striatum
(caudate +
putamen)
Figure P5.2 A photograph of the intact human brain (A) and a diagram showing some of
the large subcortical regions (B).
The photograph (A) shows the surface dominated by the convoluted cortex. The area at the bottom on
the right is the cerebellum, and beneath this can be seen the beginnings of the spinal cord where it was
separated. The cortex is illustrated in the diagram (B), and beneath this the presence of some of the
larger subcortical regions referred to later in this section.
A: Corbis/Digital Stock.
P5.5 Regions are overlaid with different neurotransmitters 405
We are used to the notion that the higher intellectual functions of the brain occur in the
cortex—it is worth noting that the cortex is in intimate and two-way contact with the
subcortical regions of the brain, and that the ‘higher functions’ are profoundly influenced
by these subcortical regions. A good example is the hippocampus and its involvement in
memory recall—disturbance of hippocampal function occurs in Alzheimer’s disease, and
this contributes to memory deficits. The limbic system incorporates several regions,
including the hippocampus, amygdala, hypothalamus, and nucleus accumbens, and
is conventionally associated with emotions and diverse advanced mental functions. We
encounter these limbic regions in Chapter 18, particularly in relation to schizophrenia and
its treatment. The hypothalamus also plays a major role in assembling information from
various parts of the brain into an action plan for the endocrine system—note its closeness,
at the base of the brain, to the pituitary. There is a term ‘basal ganglia’ that cannot be
entirely ignored—it incorporates fairly large structures lying beneath the cortex, which
include parts called the caudate and putamen, which together form the striatum. This
collection of connected regions is involved in the planning of physical movement of the
body, and degeneration of a set of neurons here is the central cause of Parkinson’s
disease, as discussed in Chapter 17.
P5.5 Regions are overlaid with different
neurotransmitters
The regions of the brain are all complex networks in which neurons may be intrinsic
(interneurons—beginning and ending in a single region), or connecting (projection
neurons—beginning in one region and ending in another). These neurons are
characterized by their principal neurotransmitters. In addition to glutamate and GABA,
there are also neurons using diverse modulatory neurotransmitters. These include the
monoamine neurotransmitters (e.g. dopamine and noradrenaline) and the indoleamine
5-hydroxytryptamine (5-HT or serotonin), each with vast applications in
neuropharmacology and the treatment of diseases of the brain. When we consider that
the number of different neurotransmitters is counted in hundreds, and that many (most) of
these interact with several receptor subtypes, the number of different synaptic contacts
defined by neurotransmitter–receptor pairing alone is enormous. This contributes to the
extraordinary complexity of brain neuronal networks. Many of the neurotransmitters—their
synthesis, storage, release, removal, and receptors—are the targets of drugs used in
neurology and psychiatry. We shall now enter this exciting world of brain disorders, pain,
unhappiness, and insanity.
Chapter 16
Epilepsy
Useful terms for this topic
Absence seizure: A generalized seizure without signs
of convulsions, characterized by a short period of
blank staring and unresponsiveness.
Epilepsy: Any neurological disorder that is
characterized by recurrent seizures.
Generalized seizure: A seizure involving large
populations of neurons in both hemispheres of the
brain.
Partial seizure: A seizure where initial abnormal ring
is limited to a specic area in one hemisphere of the
brain, but which can spread and become generalized.
Seizure: Abnormal synchronous ring of large
ensembles of neurons.
Status epilepticus: A potentially life-threatening state
in which seizures occur continuously without recovery
of consciousness in between.
Tonic–clonic seizure: A generalized seizure composed
of two phases: a brief tonic phase with body stiffness,
followed by the clonic phase, characterized by full body
spasm with intermittent relaxations.
e most common conception of epilepsy is of a disease
that results in ts (or seizures) consisting of gross
movements of the whole body, with uncontrolled
contractions of the limbs and facial muscles. But what
about someone who has repeated episodes of blank
staring, in which mental activity and engagement with the
outside world seem to have departed? Such ‘absence’
seizures are a common manifestation of epilepsy.
Recurrent episodes of memory recollection, which
overwhelm and occupy the entire mind, could also be
due to an epileptic t. What these and other seizures have
in common is that they are caused by a transient period of
uncontrolled neuronal excitation, with disordered waves
of activity disrupting normal function in a part, or all, of
the brain. Seizures may be rare and mild, or major and
disruptive of normal life, and in an extreme form they can
be life-threatening. ey may remain or develop over a
lifetime, or they may subside as the years pass. ey may
be banished, or their impact moderated, by drugs, but
they can also be drug resistant.
is diversity in clinical features is matched by the range
of drugs available to treat epilepsy, as we shall see later.
e pattern of drugs used is largely governed by clinical
experience rather than by a full understanding of their
neuropharmacological mechanisms of action.
Nevertheless, aided by diagnostic methods, including
electroencephalography (EEG), we now understand that
the dysfunction in epilepsy is a failure to control neuronal
excitability in the brain, and that the dierent cellular and
molecular actions of antiepileptic drugs moderate this
dysfunction in various ways. is enables a more eective
understanding of patients’ responses, or lack of
responses, and a logical approach to combining dierent
drugs. Some of the complexities of managing this
condition are illustrated by the patient Ambreen in
Workbook 13 at the end of this chapter.
16.1 What is epilepsy? Seizures and convulsions: prevalence,
types, and causes
Epilepsy is diagnosed when patients suer repeated
epileptic seizures. ese seizures are sudden episodes of
abnormal bursts of excitatory brain activity, leading to
transient motor, autonomic, psychic, or sensory
dysfunction. Seizures can be convulsive, with gross
uncontrolled physical movements, or non-convulsive, as
408 Chapter 16 Epilepsy
in periods of blank staring behaviour (absence seizures).
Epilepsy (particularly as absence seizures) commonly
presents in childhood.
It should be noted that there are other causes of
seizures, such as childhood febrile convulsions caused
by a rapid rise in body temperature, seen when a young
child develops a fever. Ambreen, our patient in the
workbook at the end of this chapter, has a medical
history that includes childhood febrile convulsions and
‘absences’. At the age of 23, she presents with tonic–
clonic convulsions (see below), which are treated as a
rst, unexplained, appearance of epilepsy. Her
childhood experiences are not thought to have been
manifestations of epilepsy. While convulsions are
always of concern and require medical intervention,
childhood febrile convulsions are not sucient grounds
for diagnosing epilepsy. In addition, some events that
are not seizures oer potential for confusion. For
example syncope, or fainting, can be mistaken for a
seizure.
Young people with epilepsy often grow out of the
condition, eventually being able to give up antiepileptic
drugs (AEDs) for ever. is is worth noting when
counselling patients and their relatives.
16.1.1 Prevalence
Epilepsy is one of the most common neurological
conditions encountered in children and adults.
Globally, the prevalence of active epilepsy is estimated
at between 0.5% and 1%, with up to 5% of people
suering at least one seizure in their lifetime. e
incidence is higher in the rst two decades of life, drops
over the next few, before rising again in later years due
to increased neurodegenerative disease in the elderly. A
study in the USA found that 11% of elderly nursing
home residents were being prescribed AEDs.
Prescription rates of AEDs, however, do not accurately
reect the numbers aected, as some of these drugs are
used for other indications such as bipolar illness
(Chapter 19), neuropathic pain, and prophylaxis of
migraine (Chapter 20). Nevertheless, around 50–100
million people worldwide suer from epilepsy. e
condition remains dicult to treat despite the
introduction of various new drugs in the last 15 years;
30–40% of patients continue to have ts, despite drugs
and/or surgery. It is also worth noting that the objective
of drug therapy is to prevent symptoms (seizures), and
not to tackle the underlying disorder.
16.1.2 Classification of epilepsies is by
type and pattern of seizures
e term epilepsy covers a variety of conditions that are
recognized as diverse in terms of:
• causes
• cellular and molecular dysfunction providing the
conditions in which seizures can emerge
• localization of abnormal neuronal activity within the
central nervous system
• clinical manifestation of seizures.
In clinical practice, determining the type of epilepsy
present is based on the sort of seizure and whether it is
localized in origin (partial), or involves all of the brain
from the outset (primary generalized), as set out in
Figure 16.1. In addition to these categories, seizures are
described as simple if consciousness is not lost, or
complex if consciousness is lost.
Partialseizures
A partial (or focal) seizure is one that begins in a specic
region of the brain. e activity may (a) remain localized,
(b) spread to adjacent regions of the brain, or (c) spread
throughout the cerebrum. e last two cases are then
described as secondarily generalized tonic–clonic
seizures (see below).
An example is temporal lobe epilepsy, which is both
common and dicult to control with drugs. It may
remain localized, or it may spread.
Simple partial seizures e temporal lobe is itself
divided into discrete regions with distinct functions,
including a region of the cortex (neocortex), and the
regions beneath, namely the hippocampus and the
closely associated amygdala. Simple partial seizures
remain highly localized, only aecting a part of the
temporal lobe, and, depending on the area of the lobe
aected, can give rise to a range of experiences. ese
include smells, emotions, recall of past events, loss of
memory, religious experience, and sensation of feelings
in discrete regions of the body.
Complex partial seizures ese comprise abnormal
neuronal activity which spreads throughout the entire
temporal lobe. is causes a loss of ability to function that
may manifest itself either as a limited loss of
consciousness with inability to respond to others, or
bizarre mental experiences and behaviours.
16.1 What is epilepsy? 409
No prior
seizure
record
Entire
brain
Generalized
seizures
Childhood
febrile
convulsions
Repeated
seizures
EPILEPSY
Mostly
No epilepsy
Partial seizure
Remains localized
e.g. temporal lobe
Cortex Hippocampus/amygdala
Figure 16.1 Schemeoftypesofseizureactivitycommonlyseeninepilepsy.
Febrile convulsions are placed separately on the left—these are not epilepsy. Epilepsy
is characterized by repeated seizure activity, either localized or affecting the entire brain
(generalized).
Secondarily generalized tonic–clonic seizures ese
occur when the neuronal activity spreads widely
throughout the brain. eir features are described below.
It is of interest to note here that a patient may describe a
set of experiences (the aura) coming before a full epileptic
t. is arises from simple/complex partial seizure
activity which precedes the spread to a generalized
tonic–clonic phase, the t itself.
Primarygeneralizedseizures
ese are seizures with activity widely spread throughout
the brain from the outset. We can divide them into several
subcategories. e main ones useful for understanding
drug action are as follows.
Primary generalized tonic–clonic seizures involve
widespread gross muscular activity in the limbs, face, and
elsewhere. A severe attack will typically have the following
features.
• e short tonic phase (usually less than 30–40 seconds)
comprises contracted muscles, with extended head and
neck, open eyes, and straight limbs. e patient falls to
Absence
seizures
Spreads
Tonic–clonic
seizures
Occipital
lobe
Parietal
lobe
Temporal
lobe
Frontal
lobe
the ground, the body stiens, breathing becomes
laboured or ceases, and incontinence sometimes
occurs.
• e more sustained clonic phase may last for 30
minutes, but is usually much shorter. Rhythmic
contractions and relaxation of muscles generate gross
uncontrolled body movements (e.g. of face and limbs),
resulting in widespread convulsions. Coordination of
respiratory muscle contraction is lost, which together
with the prior eects on breathing during the clonic
phase results in cyanosis (blue coloration of the skin
due to low oxygen saturation of the blood).
Absence seizures commonly involve widespread
neuronal excitation from the outset, giving a short period
of blank staring and unresponsiveness which commonly
lasts 10 seconds or less. ere is no accompanying
movement of face and limbs, and posture is retained.
Absence seizures often present in childhood and can be
frequent.
Myoclonic seizures are relatively rare, involving a very
brief spasmodic contraction of muscles, resulting in jerky
410 Chapter 16 Epilepsy
movements. ey are often associated with
neurodegenerative type diseases such as multiple
sclerosis, Parkinson’s disease, and Alzheimer’s disease.
Continuousseizures
e seizures described above are episodic, meaning of
short duration (e.g. less than 5 minutes, and often a lot
shorter) with a gap (very variable, sometimes minutes but
perhaps weeks) before the onset of the next. With status
epilepticus, however, the seizure activity is of long
duration. If convulsive, such continuous seizures
represent a potentially life-threatening medical
emergency.
As described in Section 16.4, some drugs are used to
prevent all classes of seizure activity, whereas others are
only useful against particular types.
The role of electroencephalograms and brain scans
Electroencephalograms (EEGs) are recordings of brain
electrical activity taken from surface electrodes placed on
the head. Electroencephalography is a central tool used in
the diagnosis of epilepsy. It provides information for the
neurologist that contributes to the diagnosis and an
understanding of the type of seizure activity and its
approximate localization (e.g. if partial or generalized).
While EEG only oers a rough localization of epileptic
focus, this can then be further rened using
magnetoencephalography (MEG), a more recently
developed scanning method based on the magnetic
elds generated by neuronal activity.
In some patients epilepsy develops because of a brain
tumour or the presence of scar tissue caused by a
previous brain injury. ese types of epilepsy can be
successfully diagnosed with magnetic resonance imaging
(MRI), or with the more recently introduced positron
emission tomography (PET) scan.
16.1.3 Causes of epilepsy: most cases
are idiopathic
We can divide the causes of epilepsy into three areas.
• An inherited component—primary generalized
epilepsy may often be familial, but in a complex and
multifactorial way (i.e. most genes involved remain
unidentied). is often makes the genetic origins
unclear. Nevertheless, if both parents have epilepsy,
there is an increased probability of ospring being
aected.
• Non-structural metabolic causes—where identied
these may, for example, be related to alcohol abuse or
hypoglycaemia.
• Physical damage to brain regions, possibly caused by
trauma, ischaemia (brain cell death due to
inadequate oxygen supply, as in stroke),
neurodegenerative diseases (e.g. Parkinson’s
disease), or tumours.
However, in reality most cases of epilepsy must be called
idiopathic, meaning of no known cause. Many of these
cases may well fall into the rst category above, but if so
the genetic cause remains unknown.
Interictal EEGs are recordings made between seizures
which can reveal abnormalities, and so may be a useful
aid to diagnosis. Rapid, repetitive, and synchronized
discharges, clearly seen on an EEG trace as large
repetitive waves, are characteristic of epileptic seizures
and may help to distinguish between the dierent types.
Interestingly, such waves are characteristically seen with
absence seizures, conrming that a pattern of
uncontrolled excitation occurs during this type of
generalized seizure.
It is important to note, however, that EEGs from some
non-epileptic patients can show abnormal patterns and,
furthermore, that some epileptic patients do not have
EEGs that are characteristic of epilepsy. Despite this,
EEGs remain a valuable aid to diagnosis, in conjunction
with a full medical history, good witness accounts of
seizures, and observations of signs and symptoms.
Our fictional patient Ambreen develops generalized
tonic-clonic seizures at the age of 23, the cause of
which is unknown—perhaps she had a genetic
pre-disposition which emerged at a certain stage
in her development, or in response to a particular
set of precipitating circumstances or environmental
insults.
It is tempting to think that we will be able to attach a
cause to epilepsy that is related to its biological basis,
discussed in the next section. Our understanding of
epilepsy at a cellular and molecular level is mainly
centred on the inuence of excitatory and inhibitory
neurotransmitters. A future genetic model of epilepsy
may well explain the cause of the neurotransmitter
imbalance that lies at its heart, and possibly reveal a
more fundamental change in brain neurophysiology/
biochemistry which underlies this alteration.
16.2 The biological basis of epilepsy: brakes and accelerators 411
16.2 The biological basis of epilepsy: brakes and accelerators
Box 16.1 contains an overview of the role of the major
excitatory and inhibitory neurotransmitter systems in
the brain, with comment on how this relates to
experimental epilepsy (where seizure activity is
intentionally generated in animals as a tool for
understanding human epilepsy). Here we note that, as
described in the introduction to this section, the brain
has a principal excitatory neurotransmitter (glutamate),
and one main inhibitory neurotransmitter
(-aminobutyric acid, GABA).
16.2.1 Glutamate
Glutamate is released from glutamatergic nerve terminals
throughout the brain. It acts as an agonist at two main
classes of receptor, ionotropic and metabotropic. Here we
focus on one of these, the ionotropic receptors, which
have an intrinsic ion channel which opens in response to
glutamate binding. e ion channels allow Na+ and Ca2+
to enter the cell, causing its depolarization; this
glutamate–ion channel system is therefore always
excitatory. ere are three types of ionotropic glutamate
receptor: N-methyl--aspartate (NMDA), -amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA),
and kainate receptors.
ese ionotropic glutamate receptors are very widespread
in brain neurons and provide the major excitatory input
to maintain brain activity. We can regard these receptors,
then, as the accelerator pedal of the brain. ey are
explored further in Box 16.1.
Unopposed, this extensive network of stimulation would
become uncontrolled, leading to waves of dysfunctional
activity, as in seizures. Fortunately, in most of us the
glutamate excitation is moderated by the inhibitory
inuence of GABA.
16.2.2 -Aminobutyric acid (GABA)
GABA is released from extensive networks of GABAergic
neurons. Like glutamate it acts on two main classes of
receptor, ionotropic and metabotropic.
1. GABAA receptors are ionotropic receptors which,
when activated in response to GABA binding, allow
inward Cl− currents. This causes hyperpolarization
of cells leading to inhibition of neuronal
excitability.
2. GABAB is a metabotropic (G-protein-coupled) receptor
which indirectly causes opening of K+ channels. e
outward ow of K+ also leads to hyperpolarization of
the cell.
e two types of GABA receptor are widespread in the
brain, and both are implicated in the action of some
AEDs, as explained below. e GABA receptors, with their
inhibitory inuence, restrain the glutamate-based
excitations and are therefore regarded as part of the
brake pedal for the brain (Box 16.1).
Given the above it is not surprising that seizure activity,
being an unrestrained disorganized excitation, is
associated with an imbalance in the glutamate/GABA
system (Figure 16.2).
16.2.3 Voltage-sensitive Na+ channels
The initiation of a seizure is largely mediated by
overactivity in glutamatergic neurons. The repeated
waves of excitation, which spread rapidly through a
neural network during a seizure, require abnormally
high frequencies of action potential firing in these
glutamatergic neurons. This in turn requires rapid and
repeated opening of fast voltage-sensitive Na+
channels. Box 16.2 reminds us that after opening, these
Na+ channels again close (contributing to the
downward depolarizing phase). At this point, they are
for a moment not able to be opened (they are
refractory). The number of channels in this refractory
state at any point in time is proportional to the firing
rate of cells. Drugs that bind selectively to this
refractory state will cause the accumulation of
channels that are unavailable for opening. As explained
in Box 16.2, such drugs will selectively affect high
frequency firing of action potentials, whilst leaving
normal firing rates unaffected. Some AEDs act in this
way. The neurophysiology of the voltage-sensitive Na+
channels therefore helps us to understand the action of
some drugs which are very useful in the treatment of
epilepsy.
16.2.4 Voltage-sensitive Ca2+ channels
ese channels are involved in the propagation of rapid
periodic bursts of excitation. ey are located at the cell
surface, and so their opening in response to membrane
depolarization allows Ca2+ to ow into the cell down its