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Chapter 8
Part 4
Neurotransmitters
Neurotransmitter Synthesis
– Occurs either in cell body or axon terminal
– Axon terminal lacks organelles for protein synthesis
– Polypeptide/protein neurotransmitters and enzymes
must be made in the cell body and transported to the
axon terminal
– Enzymes move by slow axonal transport
– Neurotransmitters move by fast axonal transport
Neurotransmitter Release (Fig. 8-21, p. 275)
When an AP reaches the axon terminal
– Voltage-gated Ca++ channels open
– Ca++ ions move into the cell (axon terminal)
– Ca++ ions bind to regulatory proteins and initiate
exocytosis
– Synaptic vesicle fuses with cell membrane
– Fused area opens, neurotransmitter (inside synaptic
vesicle) moves out into the synaptic cleft
– Diffuses across the cleft
– Binds with a receptor on the other side
– Binding initiates a response
Figure 8-21, overview
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Neurocrine Signal Molecules (p. 275)
These are stored in the synaptic vesicles of the axon
terminal
Include neurotransmitters, neuromodulators and
neurohormones
Chemical composition is varied
“The number of molecules identified as neurotransmitters
and neuromodulators is large and growing daily”
3 kinds of Neurocrines
Neurotransmitters
– Rapid effect
– Diffuses across a synapse to a target cell
Neuromodulators
– Slow effect
– Acts either on cell which secreted it or on
neighboring cells
Neurohormones
– Once released by neuron, these diffuse into the blood
Neurotransmitters and Neuromodulators can act as
either:
Paracrine Signals
– Target cells are located close to the neuron which
secreted these
or
Autocrine signals
– Act on the cell that secreted them
“The array of neurocrines in the body is truly
staggering” (p. 275)
See Table 8-4, p. 276
7 classes of neurocrines (based on structure):
1. Acetylcholine
2. Amines
3. Amino Acids
4. Peptides
5. Purines
6. Gases
7. Lipids
Table 8-4, part 1
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Table 8-4, part 2
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Table 8-4, overview
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1. Acetylcholine (ACh)
Neurons that secrete ACh and receptors that bind
ACh are called cholinergic
Myasthenia gravis: disease in which the immune
system fails to reecognize (as self) the ACh
receptors of skeletal muscle (p. 278)
2. Amines
All active in the CNS
Norepinephrine is the major neurotransmitter in the
PNS
2. Amines (continued)
Each of these are derived from a single amino acid
Example: tyrosine can be converted to dopamine, or
norepinephrine, or epinephrine
These 3 can be neurotransmitters or neurohormones
(when secreted by adrenal medulla)
drenergic or noradrenergic
Neurons that secrete norepinephrine
2. Amines (continued)
This name (adrenergic) comes from the early 20th
century British researchers. They thought that
sympathetic neurons secreted adrenaline
(epinephrine) and so named the neurons
adrenergic
Serotonin (5-hydroxytryptamine or 5-HT)
Another amine neurotransmitter
Made from the amino acid tryptophan
Serotonergic neurons—secrete serotonin
Table 8-4, part 1
Copyright © 2010 Pearson Education, Inc.
2. Amines (continued)
Histamine
Another amine neurotransmitter
Made from the amino acid histadine
3. Amino Acids
At least 4 function as neurotransmitters in the CNS:
Glutamate (glutaminergic neuron/receptor): primary
excitatory neurotransmitter (CNS)
Aspartate: same function as glutamate in selected
brain regions
3. Amino Acids (continued)
GABA (gamma-aminobutyric acid):
Main inhibitory neurotransmitter in the brain
Glycine:
Primary inhibitory neurotransmitter in the spinal
cord
Also, potentiates (see next slide) the excitatory
effects of glutamate at one type of glutamate
receptor
Figure 7-18
Synergism or
Potentiation
(p. 234)
The combined effects
are greater than the
sum of the individual
actions
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Agonist
A molecule that combines with a receptor and mimics a
response
Antagonist:
One substance opposes the action of another
For more details, see p. 395 and Table 11-3
4. Peptides
Lots of different neurotransmitters and
neuromodulators are peptides:
Substance P: involved in some pain pathways
Opioid peptides (enkephalins and endorphins):
These mediate pain relief or analgesia
Cholecystokinin (CCK) and Atrial natriuretic peptide
Function as both neurohormones and
neurotransmitters
5. Purines
Adenosine
Adenosine monophosphate (AMP)
Adenosine triphosphate (ATP)
All 3 above can act as neurotransmitters
They bind to purinergic receptors in the CNS and
also in the heart
6. Gases
Nitric Oxide (NO)
An unstable gas, synthesized from oxygen and the
amino acid arginine
When acting as a neurotransmitter, it diffuses freely
into a cell rather than bind to a membrane receptor
Once inside the cell, it binds to a protein
Has a half-life of 2-30 seconds, very hard to study
Can also be released by cells other than neurons,
acts as a paracrine in this case
6. Gases (continued)
Carbon monoxide (CO) and hydrogen sulfide (H2S)
Recent work has shown that these two toxic gases
are produced in tiny amounts in the body to serve
as neurotransmitters
7. Lipid Neurocrines
Eicosanoids (p.31) are 20-carbon fatty acids, found
in animals
Eikos = twenty
Eicosanoids are regulators of various physiological
functions
Examples: Thromboxanes, leukotrienes,
prostaglandins
7. Lipid Neurocrines (continued)
Several eicosanoids are endogenous ligands for
cannabinoid receptors
Endogenous: “originates within”
CB1 cannabinoid receptor is found in the brain
CB2 cannabinoid receptor is found on immune cells
The receptors were named for one of their
endogenous ligands: THC which comes from the
plant Cannabis sativa or marijuana
Multiple Receptor Types
All neurotransmitters (except NO) bind to one or more
receptor types
Each receptor type may have multiple subtypes, allowing
one neurotransmitter to to have different effects in
different tissues
Receptor subtypes are distinguished by letter and number
subscripts
Multiple Receptor Types
Receptor subtypes are distinguished by letter and number
subscripts:
Serotonin (5-HT) has at least 20 receptor subtypes:
5-HT1A
5-HT4
etc.
Membrane Receptor Categories (p. 182)
Neurotransmitter receptors are of two types:
Ligand-gated ion channels
And
G protein-coupled receptors (GPCR)
Lots of current research on both of these (see p. 279 for
details)
Figure 6-5
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Ionotropic receptors
These alter ion channel function
Metabotropic receptors
These work through second-messenger systems
Some metabotropic GPCRs regulate opening and closing
of ion channels
Agonist
A molecule that combines with a receptor and mimics a
response
Antagonist:
One substance opposes the action of another
For more details, see p. 395 and Table 11-3
Cholinergic receptors (2 main types)
Nicotinic
– Nicotine is an agonist for this one
– Found on skeletal muscle, in the autonomic division
of the PNS, also found in the CNS
– Receptors are monovalent cation channels (Na+, K+)
– Na+ entry into cells here exceeds K+ entry
Cholinergic receptors (2 main types)
Muscarinic
– Muscarine (from fungi) is an agonist for this one
– 5 related subtypes
– All are coupled to G proteins and linked to second
messengers
– Tissue response varies with receptor subtype
– Occur in CNS and in autonomic parasympathetic
division of PNS
Adrenergic receptors
– Two classes: alpha and beta, multiple subtypes
– All are coupled to G proteins and linked to second
messengers
– The two classes, alpha and beta, work through
different second messenger pathways
Glutaminergic receptors
– Glutamate is the main excitatory neurotransmitter in
the CNS
– Action of glutamate at a particular synapse depends
on the receptor type on the target cell
– AMPA receptors
» Ligand-gated monovalent cation channels
(similar to nicotinic acetylcholine channels)
Glutaminergic receptors (continued)
– Action of glutamate at a particular synapse depends
on the receptor type on the target cell
– NMDA receptors
– These are unusual
– Cation channels (for Na+, K+, Ca++)
– Channel opening requires both glutamate
binding and change in membrane potential
– At RMP, channel is blocked by a Mg++ ion
Postsynaptic responses
Fast synaptic potential
– Neurotransmitter binds to and then opens a receptorchannel on the postsynaptic cell
– This leads to ion movement and a change in
membrane potential
– Excitatory postsynaptic potential (EPSP)
– Depolarizing, more likely to fire an AP
– Inhibitory postsynaptic potential (IPSP)
– Hyperpolarizing, less likely to fire an AP
Slow synaptic potential
Use second messengers, therefore, take longer to create
the response
Also, the response lasts longer
In addition to working on ion channels, these responses
may modify existing cell proteins or regulate the
production of new cell proteins
Found in growth and development of neurons and may be
a mechanism in long-term memory
Figure 8-23
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Neurotransmitter Activity is rapidly terminated
Neurotransmitters, once they cross the cleft and bind, can
then be recycled or reused
See next two slides
Figure 8-22, overview
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Figure 8-24, overview
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Integration of Neural Information Transfer
Divergence (Fig. 8-25a, p. 282)
– When a presynaptic neuron branches and its
collaterals synapse on to multiple target neurons
Convergence (Fig. 8-25b, p. 282)
– When a group of presynaptic neurons provide input
to a smaller number of postsynaptic neurons
Combinations of the above (in the CNS) can result in one
postsynaptic neuron with synapses from 10,000+
presynaptic neurons
Figure 8-25
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Figure 8-26
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Spatial Summation (Fig. 8-28a)
– Initiation of an AP from several nearly simultaneous
graded potentials
Temporal Summation (Fig. 8-29)
– Summation that occurs from graded potentials
overlapping in time
Figure 8-28a, overview
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Postsynaptic inhibition (Fig. 8-28b)
– A presynaptic neuron releases an inhibitory
neurotransmitter onto a postsynaptic cell and alters
its response
Figure 8-28b, overview
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Temporal Summation (Fig. 8-29)
– Summation that occurs from graded potentials
overlapping in time
Figure 8-29
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Figure 8-31a, overview
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Figure 8-31b, overview
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