Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 6

Synaptic & Junctional Transmission 117

neuropeptides. The vesicles and the proteins contained in their
walls are synthesized in the neuronal cell body and transported
along the axon to the endings by fast axoplasmic transport. The
neuropeptides in the large dense-core vesicles must also be pro-
duced by the protein-synthesizing machinery in the cell body.
However, the small clear vesicles and the small dense-core vesi-
cles recycle in the nerve ending. These vesicles fuse with the cell
membrane and release transmitters through exocytosis and are
then recovered by endocytosis to be refilled locally. In some
instances, they enter endosomes and are budded off the endo-
some and refilled, starting the cycle over again. The steps
involved are shown in Figure 6–4. More commonly, however,
the synaptic vesicle discharges its contents through a small hole

in the cell membrane, then the opening reseals rapidly and the

main vesicle stays inside the cell (kiss-and-run discharge). In this

way, the full endocytotic process is short-circuited.

The large dense-core vesicles are located throughout the pre-

synaptic terminals that contain them and release their neu-

ropeptide contents by exocytosis from all parts of the terminal.

On the other hand, the small vesicles are located near the syn-

aptic cleft and fuse to the membrane, discharging their contents

very rapidly into the cleft at areas of membrane thickening

called

active zones

(Figure 6–3). The active zones contain

many proteins and rows of calcium channels.

The Ca

2+

that triggers exocytosis of transmitters enters the pre-

synaptic neurons, and transmitter release starts within 200

μ

s.

Therefore, it is not surprising that the voltage-gated Ca

2+

channels

are very close to the release sites at the active zones. In addition,

for the transmitter to be effective on the postsynaptic neuron

requires proximity of release to the postsynaptic receptors. This

orderly organization of the synapse depends in part on

neurexins,

proteins bound to the membrane of the presynaptic neuron that

bind neurexin receptors in the membrane of the postsynaptic

neuron. In many vertebrates, neurexins are produced by a single

gene that codes for the

α

isoform. However, in mice and humans

they are encoded by three genes, and both

α

and

β

isoforms are

produced. Each of the genes has two regulatory regions and

extensive alternative splicing of their mRNAs. In this way, over

1000 different neurexins are produced. This raises the possibility

that the neurexins not only hold synapses together, but also pro-

vide a mechanism for the production of synaptic specificity.

As noted in Chapter 2, vesicle budding, fusion, and dis-

charge of contents with subsequent retrieval of vesicle mem-

brane are fundamental processes occurring in most, if not all,

cells. Thus, neurotransmitter secretion at synapses and the

accompanying membrane retrieval are specialized forms of the

general processes of exocytosis and endocytosis. The details of

the processes by which synaptic vesicles fuse with the cell

membrane are still being worked out. They involve the

v-snare

protein

synaptobrevin

in the vesicle membrane locking with

the

t-snare

protein

syntaxin

in the cell membrane; a multipro-

tein complex regulated by small GTPases such as rab3 is also

involved in the process (Figure 6–5). The synapse begins in the

presynaptic and not in the postsynaptic cell. The one-way gate

at the synapses is necessary for orderly neural function.

Clinical Box 6–1 describes the how neurotoxins can disrupt

transmitter release in either the CNS or at the neuromuscular

junction.

ELECTRICAL EVENTS IN

POSTSYNAPTIC NEURONS

EXCITATORY & INHIBITORY

POSTSYNAPTIC POTENTIALS

Penetration of an

α

-motor neuron is a good example of the

techniques used to study postsynaptic electrical activity. It is

FIGURE 6–3
Axodendritic, axoaxonal, and axosomatic
synapses.
Many presynaptic neurons terminate on dendritic spines,
as shown at the top, but some also end directly on the shafts of den-
drites. Note the presence of clear and granulated synaptic vesicles in
endings and clustering of clear vesicles at active zones.

Presynaptic

cell

Postsynaptic

cell

Axo-axonal

Microtubules

Mitochondria

Clear vesicles

Active zone

Axon

Axodendritic

Axodendritic

Postsynaptic

density

Soma

Axosomatic

Dendrite

Dendritic spine