Neurosciences – Chapter 6 – neurotransmitters and their receptors
Categories of neurotransmitters
2 categories of neurotransmitters based on size
1. Neuropeptides (peptide neurotransmitters); large transmitter composed of 3 to
36 amino acids
2. Small-molecule neurotransmitter
a. Acetylcholine
b. Amino acids (glutamate, aspartate,
GABA, glycine)
c. Purine
d. Biogenic amines; separate group
because of their similar chemical
properties and postsynaptic actions
Neurotransmitter receptors:
1. Ionotropic neurotransmitter receptor (ligand-
gated ion channel)
2. Metabotropic neurotransmitter receptors (G-protein coupled receptors)
Acetylcholine
Serves as neurotransmitter at skeletal neuromuscular
junctions and at neuromuscular synapse
Function of ACh;
1. Heart muscle cell: decrease rate and force of
contraction (muscarine 2 receptor)
2. Skeletal muscle cell: contraction (nicotine
receptor)
3. Salivary gland cell: secretion (muscarine 1
receptor)
Synthesis and breakdown Ach:
Synthesis: Acetyl CoA+ choline -->
acetylcholine. By choline acetyltransferase
(ChAT) = rate-limiting step
Acetyl CoA; from glucose to pyruvate to acetyl
CoA
Choline; present in plasma at high
concentration, it is taken up into cholinergic
neurons by high-affinity, Na dependent choline
co-transporter (ChT)
After synthesis: vesicular ACh transporter (VAChT) load Ach into cholinergic vesicle.
The energy required to concentrate ACh in vesicle provided by the acid pH of the
vesicle, which allows VAChT to exchange H+ for ACh
Breakdown: Acetylcholine --> acetate + choline. By acetylcholinesterase (AChE)
, Important because when ACh accumulate it depolarizes the postsynaptic muscle cell
and render it refractory (maakt het ongevoelig) to subsequent ACh release. Causing
neuromuscular paralysis.
Neurotransmitter receptor;
1. Nicotinic ACh receptor (nAChR)--> Ionotropic
neurotransmitter receptor (ligand-gated ion channel)
Channels that generate excitatory postsynaptic responses
Large protein complexes consisting of 5 subunits: alfa,
beta, gamma, omega and epsilon. Combination of 3-5
required for each receptor type.
Neuromuscular junction: 2x alfa, 1x beta, 1x
omega, 1x gamma or episilon
Neuron-neuron synapse: 3x alfa, 2x beta
This general arrangement, several receptor
subunits coming together to form a ligand-gated
ion channel, is characteristic of all the ionotropic
receptors. The amount and type of subunits the
receptors have can be different for each
neurotransmitter.
2. Muscarinic ACh receptor (mAChR) --> Metabotropic
neurotransmitter receptors (G-protein coupled receptors
(GPCR))
Mediate most of the effects of ACh in the brain
It has 7 helical membrane-spanning domains.
G-protein complex consist of: alfa, beta and gamma
Activation changes GDP to GTP on the alfa subunit of the G-
protein complex
Binding of ACh to the binding site causes a conformation change that permits
G-proteins to bind to cytoplasmic domain of the receptor.
5 subtypes of mAChR are known and are coupled to different
types of G-proteins.
Multiple variants are present of metabotropic neurotransmitter
receptors
Categories of neurotransmitters
2 categories of neurotransmitters based on size
1. Neuropeptides (peptide neurotransmitters); large transmitter composed of 3 to
36 amino acids
2. Small-molecule neurotransmitter
a. Acetylcholine
b. Amino acids (glutamate, aspartate,
GABA, glycine)
c. Purine
d. Biogenic amines; separate group
because of their similar chemical
properties and postsynaptic actions
Neurotransmitter receptors:
1. Ionotropic neurotransmitter receptor (ligand-
gated ion channel)
2. Metabotropic neurotransmitter receptors (G-protein coupled receptors)
Acetylcholine
Serves as neurotransmitter at skeletal neuromuscular
junctions and at neuromuscular synapse
Function of ACh;
1. Heart muscle cell: decrease rate and force of
contraction (muscarine 2 receptor)
2. Skeletal muscle cell: contraction (nicotine
receptor)
3. Salivary gland cell: secretion (muscarine 1
receptor)
Synthesis and breakdown Ach:
Synthesis: Acetyl CoA+ choline -->
acetylcholine. By choline acetyltransferase
(ChAT) = rate-limiting step
Acetyl CoA; from glucose to pyruvate to acetyl
CoA
Choline; present in plasma at high
concentration, it is taken up into cholinergic
neurons by high-affinity, Na dependent choline
co-transporter (ChT)
After synthesis: vesicular ACh transporter (VAChT) load Ach into cholinergic vesicle.
The energy required to concentrate ACh in vesicle provided by the acid pH of the
vesicle, which allows VAChT to exchange H+ for ACh
Breakdown: Acetylcholine --> acetate + choline. By acetylcholinesterase (AChE)
, Important because when ACh accumulate it depolarizes the postsynaptic muscle cell
and render it refractory (maakt het ongevoelig) to subsequent ACh release. Causing
neuromuscular paralysis.
Neurotransmitter receptor;
1. Nicotinic ACh receptor (nAChR)--> Ionotropic
neurotransmitter receptor (ligand-gated ion channel)
Channels that generate excitatory postsynaptic responses
Large protein complexes consisting of 5 subunits: alfa,
beta, gamma, omega and epsilon. Combination of 3-5
required for each receptor type.
Neuromuscular junction: 2x alfa, 1x beta, 1x
omega, 1x gamma or episilon
Neuron-neuron synapse: 3x alfa, 2x beta
This general arrangement, several receptor
subunits coming together to form a ligand-gated
ion channel, is characteristic of all the ionotropic
receptors. The amount and type of subunits the
receptors have can be different for each
neurotransmitter.
2. Muscarinic ACh receptor (mAChR) --> Metabotropic
neurotransmitter receptors (G-protein coupled receptors
(GPCR))
Mediate most of the effects of ACh in the brain
It has 7 helical membrane-spanning domains.
G-protein complex consist of: alfa, beta and gamma
Activation changes GDP to GTP on the alfa subunit of the G-
protein complex
Binding of ACh to the binding site causes a conformation change that permits
G-proteins to bind to cytoplasmic domain of the receptor.
5 subtypes of mAChR are known and are coupled to different
types of G-proteins.
Multiple variants are present of metabotropic neurotransmitter
receptors
