Ganong's Review of Medical Physiology, 23rd Edition

134
SECTION II
Physiology of Nerve & Muscle Cells

and anoxia, loss of neurons is increased because glutamate
reuptake is inhibited.

SMALL-MOLECULE TRANSMITTERS

Synaptic physiology is a rapidly expanding, complex field that
cannot be covered in detail in this book. However, it is appro-
priate to summarize information about the principal neu-
rotransmitters and their receptors.

MONOAMINES

Acetylcholine

Acetylcholine, which is the acetyl ester of choline, is largely
enclosed in small, clear synaptic vesicles in high concentra-
tion in the terminal boutons of neurons that release acetyl-

choline (

cholinergic

neurons). Synthesis of acetylcholine

involves the reaction of choline with acetate (Figure 7–1).

Acetylcholine is the transmitter at the neuromuscular junc-

tion, in autonomic ganglia, and in postganglionic parasympa-

thetic nerve-target organ junctions and some postganglionic

sympathetic nerve-target junctions. It is also found within

the brain, including the basal forebrain complex and pon-

tomesencephalic cholinergic complex (Figure 7–2). These

systems may be involved in regulation of sleep-wake states,

learning, and memory.

Cholinergic neurons actively take up choline via a trans-

porter (Figure 7–4). Choline is also synthesized in neurons.

The acetate is activated by the combination of acetate groups

with reduced coenzyme A. The reaction between active ace-

tate (acetyl-coenzyme A, acetyl-CoA) and choline is catalyzed

by the enzyme

choline acetyltransferase.

This enzyme is

found in high concentration in the cytoplasm of cholinergic

FIGURE 7–3
Fate of monoamines secreted at synaptic junctions.
In each monoamine-secreting neuron, the monoamine is synthesized
in the cytoplasm and the secretory granules
(1)
and its concentration in secretory granules is maintained
(2)
by the two vesicular monoamine
transporters (VMAT). The monoamine is secreted by exocytosis of the granules
(3),
and it acts
(4)
on receptors (Y-shaped structures labeled R).
Many of these receptors are postsynaptic, but some are presynaptic and some are located on glia. In addition, there is extensive reuptake into the
cytoplasm of the presynaptic terminal
(5)
via the monoamine neurotransmitter transporter (NTT) for the monoamine that is synthesized in the
neuron.
(Reproduced with permission from Hoffman BJ, et al: Distribution of monoamine neurotransmitter transporters in the rat brain. Front Neuroendocrinol 1998;19:187.)

2

1

3

5

4

4

Transmitter

synthesis NTT

Amino acid

precursor

Presynaptic

terminal

K+

Na+

R

R

Second

+ Other messengers

receptors

Postsynaptic

terminal

Neuron

Neuron

Glial cell

R

VMAT

H+

Cl−