Presynaptic

neuron

Connexins
Connexon

Presynaptic
membrane

Nerve
impulse
3.5 nm

Gap junction

Postsynaptic neuron

Channel formed
by pores in
each membrane

Postsynaptic
membrane
(a) An electrical synapse

20 nm

(b) Gap junctions

FIGURE 13-15 An Electrical Synapse. (a) In electrical synapses, the presynaptic and postsynaptic
neurons are coupled by gap junctions, which allow small molecules and ions to pass freely from the cytosol of
one cell to the next. When an action potential arrives at the presynaptic side of an electrical synapse, the depolarization spreads passively, due to the flow of positively charged ions, across the gap junction. (b) The gap
junction is composed of sets of channels. A channel is made up of six protein subunits, each called a connexin.
The entire set of six subunits together is called a connexon. Two connexons, one in the presynaptic membrane
and one in the postsynaptic membrane, make up a gap junction.

In a chemical synapse, the presynaptic and postsynaptic neurons are not connected by gap junctions,
(Figure 13-16), although they are connected by cell
adhesion proteins (which we will consider in Chapter
17). Instead, the presynaptic plasma membrane is separated from the postsynaptic membrane by a small space
of about 20-50 nm, known as the synaptic cleft. A nerve
signal arriving at the terminals of the presynaptic neuron
cannot bridge the synaptic cleft as an electrical impulse.
For synaptic transmission to take place, the electrical
signal must be converted at the presynaptic neuron to a
chemical signal carried by a neurotransmitter. Neurotransmitter molecules are stored in the synaptic boutons
of the presynaptic neuron. An action potential arriving
at the terminal causes the neurotransmitter to be secreted
into and diffuse across the synaptic cleft. The neurotransmitter molecules then bind to specific proteins embedded
within the plasma membrane of the postsynaptic neuron
(receptors) and are converted back into electrical signals,
setting in motion a sequence of events that either
stimulates or inhibits the production of an action potential in the postsynaptic neuron, depending on the kind
of synapse.
Neurotransmitter receptors fall into two broad groups:
ligand-gated ion channels (sometimes called ionotropic
receptors), in which activation directly affects the cell, and
receptors that exert their effects indirectly through a
system of intracellular messengers (sometimes called
metabotropic receptors; Figure 13-17). We will discuss
the latter category of receptors in Chapter 14; here, we

focus on ligand-gated channels. These membrane ion channels open in response to the binding of a neurotransmitter,
and they can mediate either excitatory or inhibitory
responses in the postsynaptic cell.

Neurotransmitters Relay Signals Across

Nerve Synapses
A neurotransmitter is essentially any signaling molecule
released by a neuron. Many kinds of molecules act as neurotransmitters. Most are detected by the postsynaptic cell via
a specific type of receptor; most neurotransmitters have
more than one type of receptor. When a neurotransmitter
molecule binds to its receptor, the properties of the receptor are altered, and the postsynaptic neuron responds
accordingly. An excitatory receptor causes depolarization of
the postsynaptic neuron, whereas an inhibitory receptor
typically causes the postsynaptic cell to hyperpolarize.
Although definitions vary, to qualify as a neurotransmitter, a compound must satisfy three criteria: (1) It must
elicit the appropriate response when introduced into the
synaptic cleft, (2) it must occur naturally in the presynaptic
neuron, and (3) it must be released at the right time when
the presynaptic neuron is stimulated. Many molecules
meet these criteria, including acetylcholine, a group of
biogenic amines called the catecholamines, certain amino
acids and their derivatives, peptides, endocannabinoids,
nucleotides such as ATP, some ions, and gases (such as
nitric oxide). Table 13-2 lists several common neurotransmitters; we will discuss some of them here.

Synaptic Transmission

381

Axon terminal

Synaptic vesicles

Presynaptic axon
Direction of
presynaptic
nerve impulse

Synaptic bouton

Presynaptic
membrane
Postsynaptic
membrane

Synaptic vesicles containing

neurotransmitter molecules
Dendrite

(c)

0.5 m

Mitochondrion
Synaptic vesicles
Presynaptic
membrane

Synaptic cleft

Postsynaptic dendrite

Synaptic
cleft

Neurotransmitter molecules

Postsynaptic
membrane
receptors
(a)
(b)
FIGURE 13-16 A Chemical Synapse. (a) When a nerve impulse from the presynaptic axon arrives at the
synapse (red arrow), it causes synaptic vesicles containing neurotransmitter in the synaptic bouton to fuse with
the presynaptic membrane, releasing their contents into the synaptic cleft. (b) Neurotransmitter molecules diffuse across the cleft from the presynaptic (axonal) membrane to the postsynaptic (dendritic) membrane, where
they bind to specific membrane receptors and change the polarization of the membrane, either exciting or
inhibiting the postsynaptic cell. (c) Electron micrograph of a chemical synapse (TEM). Arrows indicate a
postsynaptic density, where membrane receptors and other proteins cluster.

Neurotransmitter

EXTRACELLULAR
FLUID
Ion channel

Neurotransmitter

Receptor

Ion channel

Cell signaling
CYTOSOL
(a) Direct neurotransmitter action (ionotropic receptor)

(b) Indirect neurotransmitter action (metabotropic receptor)

FIGURE 13-17 Different Kinds of Receptors That Act at Chemical Synapses. (a) Direct neurotransmitter action. Ionotropic receptors act directly as ion channels. When they bind a neurotransmitter, they
undergo a conformational change, and ions can pass through them. (b) Indirect neurotransmitter action.
When metabotropic receptors bind neurotransmitters, they set in motion a series of cell signaling events that
indirectly lead to the opening of an ion channel. Because they act indirectly, metabotropic receptors act more
slowly than ionotropic receptors.

382

Chapter 13 Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons

Table 13-2

Different Kinds of Neurotransmitters

Neurotransmitter

Structure

Catecholamines
Acetylcholine

O
H3C

Biogenic Amines
Norepinephrine

Functional Class

CH2

N+

CH2

Excitatory to vertebrate CNS; PNS;

vertebrate neuroskeletal muscles;
excitatory or inhibitory muscular junction
at other sites

[CH3]3

HO
HO

Excitatory or
inhibitory

CNS; PNS

Generally excitatory;
may be inhibitory at
some sites

CNS; PNS

Generally inhibitory

CNS

Inhibitory

CNS; invertebrate
neuromuscular
junction
CNS; invertebrate
neuromuscular
junction
CNS

NH2

CH2

CH

Secretion Sites

OH

Dopamine

HO
HO

Serotonin

NH2

CH2

CH2

HO

N
H

Amino Acids
GABA g-aminobutyric H2N
acid

CH2

Glutamate

CH

H2N

C CH2
CH

CH2

CH2

CH2

CH2

NH2

CH2

COOH

Excitatory

COOH

COOH

Glycine

Inhibitory

H2N

CH2

Substance P

Arg

Pro

Lys

Pro

Gln

Met-enkephalin
(an endorphin)

Tyr

Gly

Gly

Phe

Met

COOH

Neuropeptides

Endocannabinoids
Anandamide

Gln

O
H
N

Gases
Nitric oxide

Phe

OH

Acetylcholine. In vertebrates, acetylcholine is the most

common neurotransmitter for synapses between neurons

outside the central nervous system (CNS), as well as for
neuromuscular junctions (see Chapter 16). Acetylcholine
is an excitatory neurotransmitter. Bernard Katz and his
collaborators were the first to make the important observation that acetylcholine increases the permeability of the
postsynaptic membrane to sodium within 0.1 msec of
binding to its receptor. Synapses that use acetylcholine as
their neurotransmitter are called cholinergic synapses.
Catecholamines. The catecholamines include dopamine
and the hormones norepinephrine and epinephrine, all
derivatives of the amino acid tyrosine. Because the cate-

Phe

Gly

Leu

Met Excitatory

CNS; PNS

Generally inhibitory

CNS

Inhibitory

CNS

Excitatory or inhibitory PNS

cholamines are also synthesized in the adrenal gland,

synapses that use them as neurotransmitters are termed
adrenergic synapses. Adrenergic synapses are found at
the junctions between nerves and smooth muscles in
internal organs such as the intestines, as well as at nervenerve junctions in the brain. The mode of action of adrenergic hormones will be considered in Chapter 14.
Amino Acids and Derivatives. Other neurotransmitters

that consist of amino acids and derivatives include

histamine, serotonin, and g-aminobutyric acid (GABA), as
well as glycine and glutamate. Serotonin functions in the
CNS. It is considered an excitatory neurotransmitter
because it indirectly causes potassium channels to close,
Synaptic Transmission

383

which has an effect similar to opening sodium channels in

that the postsynaptic cell is depolarized. However, its
effect is exerted much more slowly than that of sodium
channels. GABA and glycine are inhibitory neurotransmitters, whereas glutamate has an excitatory effect.
Neuropeptides. Short chains of amino acids called

neuropeptides are formed by proteolytic cleavage of precursor proteins. Hundreds of different neuropeptides have
been identified. Some neuropeptides exhibit characteristics similar to neurotransmitters in that they excite, inhibit,
or modify the activity of other neurons in the brain. However, they differ from typical neurotransmitters in that they
act on groups of neurons and have long-lasting effects.
Examples of neuropeptides include the enkephalins,
which are naturally produced in the mammalian brain
and inhibit the activity of neurons in regions of the brain
involved in the perception of pain. The modification of
neural activity by these neuropeptides appears to be
responsible for the insensitivity to pain experienced by
individuals under conditions of great stress or shock. The
analgesic (i.e., pain-killing) effectiveness of drugs such as
morphine, codeine, Demerol, and heroin derives from
their ability to bind to the same sites within the brain that
are normally targeted by enkephalins.
Other substances released at synapses include the lipid
derivatives known as the endocannabinoids, which inhibit
the activity of presynaptic neurons. The main endocannabinoid receptor found in the brain is also stimulated by
tetrahydrocannabinol, or THC, a substance found in plants
of the genus Cannabis. Marijuana is derived from the leaves
of the species Cannabis sativa and owes its effects to THC.

Elevated Calcium Levels Stimulate Secretion of

Neurotransmitters from Presynaptic Neurons
Secretion of neurotransmitters by the presynaptic cell is
directly controlled by the concentration of calcium ions in
the synaptic bouton (Figure 13-18). Each time an action
potential arrives, the depolarization causes the calcium
concentration in the synaptic bouton to increase temporarily due to the opening of voltage-gated calcium channels
in the synaptic boutons. Normally, the cell is relatively
impermeable to calcium ions, so that the cytosolic calcium
concentration remains low (about 0.1 m M). However, there
is a very large concentration gradient of calcium across the
membrane because the calcium concentration outside the
cell is about 10,000 times higher than that of the cytosol.
As a result, calcium ions will rush into the cell when the
calcium channels open.
Before they are released, neurotransmitter molecules
are stored in small, membrane-bounded neurosecretory
vesicles in the synaptic boutons (see Figure 13-18). The
release of calcium within the synaptic bouton has two
main effects on neurosecretory vesicles. First, vesicles held
in storage are mobilized for rapid release. Second, vesicles
that are ready for release rapidly dock and fuse with the

384

2 Depolarization opens
voltage-gated calcium channels,
allowing calcium ions to rush into
the terminal.

1 An action potential arrives

at the synaptic bouton, resulting
in a transient depolarization.

Synaptic
bouton

Voltage-gated
calcium channel
Ca2+

Postsynaptic
cell
Action
potential
Axon
3 Increasing calcium
in the synaptic
bouton induces
the secretion
of some
neurosecretory
vesicles.

Reserve
vesicles

Neurosecretory
Ca2+ vesicle
5 Neurotransmitter
diffuses across the
synaptic cleft to
receptors on the
postsynaptic cell.

Ca2+

Neurotransmitter
receptors
4 Prolonged
stimulation mobilizes
additional, reserve
vesicles.

Neurotransmitter
6 Binding of neurotransmitter to the receptor
alters its properties.
Ca2+

Ions

8 If sufficient
depolarization
occurs, an action
potential will result in
the postsynaptic cell.
Action
potential

7 Channels open, letting ions flow into the

postsynaptic cell. Depending on the ion,
channel opening leads to either
depolarization or hyperpolarization.
FIGURE 13-18 The Transmission of a Signal Across a

Synapse. When an action potential arrives at the presynaptic

bouton, a transient depolarization occurs, which leads to opening
of voltage-gated calcium channels. Calcium elevation results in
secretion of a neurotransmitter, which moves across the synapse
and binds to receptors on the postsynaptic cell. The resulting
depolarization can trigger an action potential.
www.thecellplace.com How synapses work

plasma membrane in the synaptic bouton region. During

this process, the membrane of a vesicle moves into close
contact with the plasma membrane of the axon terminal
and then fuses with it to release the contents of the vesicle.
We will now examine this process in more detail.

Chapter 13 Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons