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“Meet the neurotransmitters”
FAMILY NAME

ASSOCIATED NTs

AMINO ACIDS

glutamate, aspartate, glycine gamma-aminobutyric acid (GABA)

MONOAMINES
(BIOGENIC AMINES)

catecholamines (DA, NE, EP), indoleamines (5-HT), histamine, acetylcholine NEUROPEPTIDES

substance P, endorphins (enkephalins) . . .

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AMINO ACID NEUROTRANSMITTERS
General comments
1. Workhorses of the CNS
• The predominant type of neurotransmitters.
• As many as 90% of synapses involve four amino acid transmitters – glutamate, aspartate, GABA, or glycine.

2. Overall role
Can be excitatory (Glu, Asp) or inhibitory (GABA, Gly).

3. Receptors
Most work through ionotropic (ion channel) receptors.
Some use metabotropic receptors (i.e. linked to second messengers such as cAMP or IP3).

GLIAL CELL

PRESYNAPTIC
TERMINAL

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AA
AA

INACTIVATION
OF
AMINO ACID
TRANSMITTERS

AAMETAB
AA
AAFUNC (NT)

AA

Autoreceptors

Ionotropic receptors Metabotropic receptors POSTSYNAPTIC CELL

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GLUTAMATE
The major excitatory neurotransmitter
Widely distributed through the CNS

O

+

O

NH3

O

C

CH2 CH2 CH

C

O-

GLUTAMATE

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There are ~ 13 types of glutamate receptors known:
•
•
•
•

AMPA – Ionotropic
Kainate – ionotropic
NMDA (N-methyl-D-aspartate) – ionotropic “plus”
Metabotropic Glu receptors – at least 8 varieties

The ionotropic NMDA receptor is of great interest because it seems to be heavily involved in learning and memory.

Modulation of NMDA receptor
A coincidence detector
Glutamate

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Modulation of NMDA receptor
A coincidence detector

extracellular

extracellular

intracellular

intracellular

Glutamate

Glutamate and depolarization

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GABA
(γ-aminobutyric acid)
Major inhibitory neurotransmitter in CNS
Widely distributed through the CNS
(Important in inhibitory control of interneurons)

O
+

H 3N

CH

CH2
GABA

CH2

15

C

O-

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GABA
(γ-aminobutyric acid)

SYTHESIS

Glutamate
Glutamic acid
Decarboxylase
(GAD)

CO2

GABA

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Two families of GABA receptors
Cl-

EXTRACELLULAR

INTRACELLULAR

ION CHANNEL

GABAA RECEPTORS
Allow Cl- ions into neuron resulting in membrane hyperpolarization

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GABA

Modulation of GABAA receptor currents
Benzodiazepines and barbiturates

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Enhance the inhibitory action of GABA

ClNS ET
NS
ET
Brb

GABA
GABA

BDZ

Probability of opening
Open time

Twyman et al (1989) Ann. Neurol. 25: 213-220 (1989)

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Two families of GABA receptors
Cl-

EXTRACELLULAR

INTRACELLULAR

ION CHANNEL

GABAA RECEPTORS
Allow Cl- ions into neuron resulting in membrane hyperpolarization

GABAB RECEPTORS
• G-protein coupled, several subtypes cloned
• Connected to K+ channels to cause membrane hyperpolarization 22

“Meet the neurotransmitters”
FAMILY NAME

ASSOCIATED NTs

AMINO ACIDS

glutamate, aspartate, glycine gamma-aminobutyric acid (GABA)

MONOAMINES
(BIOGENIC AMINES)

catecholamines (DA, NE, EP), indoleamines (5-HT), histamine, acetylcholine NEUROPEPTIDES

substance P, endorphins (enkephalins) . . .

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MONOAMINES
(BIOGENIC AMINES)

PRECURSOR

TYPE

Tyrosine

Catecholamines

Dopamine
Norepinephrine
Epinephrine

Tryptophan

Indoleamines

Serotonin (5-HT)

Histidine

Histamine

Choline + acetyl CoA

Acetylcholine

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ACETYLCHOLINE
First neurotransmitter isolated – Otto Loewi

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VAGUS NERVE
STIMULATION

HEART #2
BEGINS
SLOWING
DOWN

Acetylcholine is created by choline acetyltranferase (ChAT) broken down (inactivated) by acetylcholinesterase (AChE)

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Acetylcholine receptor subtypes

Nicotinic
Acetylcholine
Receptor

Muscarinic
Acetylcholine
Receptor

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Somatic

Acetylcholine

Parasympathetic

Acetylcholine

Acetylcholine

Sympathetic

Acetylcholine

Norepinephrine

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THE NEUROMUSCULAR JUNCTION

Myasthenia Gravis
Bella
Diagnostic testing demonstrated that Bella (a 2 year old Silky Terrier) has antibodies to ACh receptors. Myasthenia gravis is suspected.
An edrophonium chloride challenge to confirm diagnosis. Edrophonium chloride is a very short acting reversible AChE inhibitor (acts only for about 5 min).

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