Principles of Chemical Synaptic Transmission
o Most neurotransmitters fall into one of three chemical categories:
o The amino acid and amine neurotransmitters are all small organic molecules
containing at least one nitrogen atom, and they are stored in and released from
o Peptide neurotransmitters are large molecules stored in and released from
Secretory granules and synaptic vesicles are frequently observed in the
same axon terminals
o Different neurons in the brain release different neurotransmitters
Fast synaptic transmission at most CNS synapses is mediated by the
amino acids glutamate (Glu), gamma-aminobutyric acid (GABA) and
The amine acetylcholine (Ach) mediates fast synaptic transimission at
all neuromuscular junctions. Slower forms of synaptic transmission in the
CNS and in the periphery are mediated by transmitters from all three
Neurotransmitter Synthesis and Storage
o Chemical synaptic transmission requires that neurotransmitters be synthesized
and ready for release.
o The synthesizing enzymes for both amino acid and amine neurotransmitters are
transported to the axon terminal, where they locally and rapidly direct transmitter
o Once synthesized in the cytosol of the axon terminal, the amino acid and amin
neurotransmitters must be taken up by the synaptic vesicles.
Concentrating these neurotransmitters is the job of transporters
o Different mechanisms are used to synthesize and store peptides in secretory
This occurs in the rough ER
Generally, a long peptide synthesized in the rough ER is split in the Golgi
apparatus, and of the smaller peptide fragments is the active
Secretory granules containing the peptide neurotransmitter bud off
the Golgi apparatus and are carried to the axon terminal by
o Neurotransmitter release is triggered by the arrival of an action potential in the
o The depolarization of the terminal membrane causes voltage-gated calcium
channels in the active zones to open.
These membrane channels are very s2+ilar to the sodium channels
o There is a large inward driving force on Ca o The resulting elevation in [Ca ]Iis the signal that causes neurotransmitter to be
released from synaptic vesicles
o The vesicle releases their contents by a process called exocytosis.
o The membrane of the synaptic vesicle fuses to the presynaptic membrane at the
active zone, allowing the contents of the vesicle to spill out into the synaptic cleft
(See Fig. 5.11.).
o Exocytosis is quick because Ca 2+enters at the active zone, precisely where
synaptic vesicles are ready and waiting2+o release their contents
o The precise mechanism by which [Ca ] stimIlates exocytosis is poor
o The speed of neurotransmitter release suggests that the vesicles involved are
those at ready “docked” at the active zones.
Docking is believed to involved interactions between proteins in the
synaptic vesicle membrane and the active zone
In the presence of high [Ca ], Ihese proteins alter their conformation so
that the lipid bilayers of the vesicle and presynaptic membranes fuse,
forming a pore that allows the neurotransmitter to escape into the cleft.
The mouth of this exocytotic fusion pore continues to expand until the
membrane of the vesicle is fully incorporated into the presynaptic
The vesicle membrane is later recovered by the process of endocytosis
and the recycle vesicle is refilled with neurotransmitter
o During periods of prolonged stimulation, vesicles are mobilized from a “reserve
pool” that is bound to the cytoskeletons of the axon terminal
The release of these vesicles from the cytoskeleton, an2+their docking to
the active zone, is also triggered by elevations of [Ca ].i
o Secretory Granules also release peptide neurotransmitters by exocytosis, in a
calcium –dependent fashion, but not at the active zones
Because the sites of granule exocytosis occur at a distance from the sites
of Ca entry, peptide neurotransmitters are usually not released in
response to every action potential invading the terminal.
Release of peptides generally requires high-frequency trains of
action potentials, so that the [Ca ] throughout the terminal can
build to the level required to trigger release away from the active
Neurotransmitter Receptors and Effectors
o Transmitter-Gated Ion Channels
Receptors known as transmitter-gated ion channels are membrane-
spanning proteins consisting of four or five subunits that come together to
form a pore between them.
In the absence of neurotransmitter, the pore is usually closed.
When neurotransmitter binds to specific sites on the extracellular
region of the channel, it induces a conformational change which
opens the pore.
Transmitter-gated channels generally do not show the same degree of ion
selectivity as do voltage-gated channels (e.g. Ach-gated ion channels are
permeable to both Na ions and K ions). As a rule, if the open channels are permeable to Na , the net effect will be
to depolarize the po