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Neurotransmitters
Dr. Surakshya Gautam
Department of Biochemistry
Objectives
Neurotransmitters : Definition, properties
Synaptic transmission
Neuromuscular transmission
Neurotransmitter receptors
Types : Acetyl choline, Dopamine, NE, E, GABA,
Serotonin, NO
Structure of neuron
Chemical
activity
Synaptic
transmission
Synaptic
cleft
Synaptic
vesicles
Neurotransmitter
Around 10,000 molecules of NT are
contained in vesicle
NEUROTRANSMITTERS
• Neurotransmitters are endogenous chemicals that
transmit signals across a synapse from one neuron (brain
cell) to another 'target' neuron.
• Neurotransmitters are packaged into synaptic vesicles
clustered beneath the membrane in the axon terminal, on
the presynaptic side of a synapse.
Criteria for Neurotransmitter
1. Must be present or synthesized within neuron
2. Must be stored within the nerve ending prior to
release, e.g. in synaptic vesicles
3. Must be released from the presynaptic ending in
response to an action potential
4. Must recognize and bind the receptors present on
the postsynaptic neuron or effector cell
5. Some mechanisms must exist for the inactivation of
the biological activity after chemical’s work is done
Classification of Neurotransmitters
Neurotransmitters can be broadly split into two groups:
• Based on chemical composition
– the ‘classical’, small molecule neurotransmitters, and
– the relatively larger neuropeptide neurotransmitters
• Based on the effect on postsynaptic end
– Excitatory
– Inhibitory
Resting membrane
potential inside the
neuron is -70mv
Excitatory
(1) Opening of Na+ channels
(2) Depressed conductance Cl- or K+ channels or both
Inhibitory
(1) Opening of Cl- ion channels through receptor.
(2) ↑ in conductance of K+ ions through the receptor.
Classical Small Molecule NTs
Type Neurotransmitter Postsynaptic effect
Choline ester Acetylcholine Excitatory
Amino acids γ-aminobutyric acid (GABA) Inhibitory
Glycine Inhibitory
Glutamate Excitatory
Aspartate Excitatory
Biogenic amines Dopamine (DA) Excitatory
Epinephrine (Epi) Excitatory
Norepinephrine (NE) Excitatory
Serotonin (5-HT) Excitatory
Histamine Excitatory
Gases Nitric oxide (NO) Excitatory and Inhibitory
Carbon Monoxide (CO) Excitatory and Inhibitory
Larger Neuropeptide NTs
Large transmitter molecules composed of 3 to 36 amino acids
1. Opioid: enkephalins; β-endorphin
2. Neurohypophyseal: vasopressin; oxytocin; neurophysins
3. Tachykinins: substance P; neurokinin A; neurokinin B
4. Gastrins: gastrin; cholecystokinins
5. Somatostatins: somatostatin 14; somatostatin 28
6. Glucagon-related: vasoactive intestinal polypeptide
7. Pancreatic-polypeptide
8. Miscellaneous: bombesin; neurotensin; bradykinin;
angiotensin; calcitonin gene-related peptide
Specific to ion
Neurotransmitter receptors
They are protein embedded in the plasma
membrane of postsynaptic cells
Domains of receptor molecules extend into the
synaptic cleft bind neurotransmitters
This will directly or indirectly cause ion channels in
the post synaptic membrane to open or close
Resulting ion fluxes will change the membrane
potential of post synaptic cell and thus mediating
the transfer of information across the synapse.
Neurotransmitter Receptors
Two main families:
A. Ionotropic receptors
ligand gated ion channels
B. Metabotropic receptors
coupled to G-protein
uses cAMP or IP3 as 2nd messenger
Ionotropic receptors
Fast acting ligand-gated
ion channels
It combine transmitter
binding and channel
function into single
entity
Multimers made up of at
least 4 or 5 individual protein
subunits, each of which
contributes to the pore of
the ion channel
Metabotropic Receptor
• Slow acting G-proteins coupled receptors
• These receptors do not have ion channels as part of
their structure; instead, they affect channels by the
activation of intermediate molecules called G-proteins
• Aks G-protein-coupled receptors
• Are monomeric proteins with an extracellular domain
that contains a neurotransmitter binding site and an
intracellular domain that binds to G-proteins.
Thus, G-proteins can be thought of as transducers that
couple neurotransmitter binding to the regulation of
postsynaptic ion channels
Most neurotransmitters can activate
multiple receptor subtypes and receptor
classes
Receptors for Various
Neurotransmitters
Steps in chemical transmission
Removal of neurotransmitters
• Diffusion away from the postsynaptic receptors, OR
• Reuptake into nerve terminals or surrounding glial
cells, OR
• Degradation by specific enzymes, OR
• Combination of these mechanisms.

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Neurotransmitters 1

  • 2. Objectives Neurotransmitters : Definition, properties Synaptic transmission Neuromuscular transmission Neurotransmitter receptors Types : Acetyl choline, Dopamine, NE, E, GABA, Serotonin, NO
  • 5. NEUROTRANSMITTERS • Neurotransmitters are endogenous chemicals that transmit signals across a synapse from one neuron (brain cell) to another 'target' neuron. • Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane in the axon terminal, on the presynaptic side of a synapse.
  • 6. Criteria for Neurotransmitter 1. Must be present or synthesized within neuron 2. Must be stored within the nerve ending prior to release, e.g. in synaptic vesicles 3. Must be released from the presynaptic ending in response to an action potential 4. Must recognize and bind the receptors present on the postsynaptic neuron or effector cell 5. Some mechanisms must exist for the inactivation of the biological activity after chemical’s work is done
  • 7. Classification of Neurotransmitters Neurotransmitters can be broadly split into two groups: • Based on chemical composition – the ‘classical’, small molecule neurotransmitters, and – the relatively larger neuropeptide neurotransmitters • Based on the effect on postsynaptic end – Excitatory – Inhibitory
  • 8. Resting membrane potential inside the neuron is -70mv
  • 9. Excitatory (1) Opening of Na+ channels (2) Depressed conductance Cl- or K+ channels or both Inhibitory (1) Opening of Cl- ion channels through receptor. (2) ↑ in conductance of K+ ions through the receptor.
  • 10. Classical Small Molecule NTs Type Neurotransmitter Postsynaptic effect Choline ester Acetylcholine Excitatory Amino acids γ-aminobutyric acid (GABA) Inhibitory Glycine Inhibitory Glutamate Excitatory Aspartate Excitatory Biogenic amines Dopamine (DA) Excitatory Epinephrine (Epi) Excitatory Norepinephrine (NE) Excitatory Serotonin (5-HT) Excitatory Histamine Excitatory Gases Nitric oxide (NO) Excitatory and Inhibitory Carbon Monoxide (CO) Excitatory and Inhibitory
  • 11. Larger Neuropeptide NTs Large transmitter molecules composed of 3 to 36 amino acids 1. Opioid: enkephalins; β-endorphin 2. Neurohypophyseal: vasopressin; oxytocin; neurophysins 3. Tachykinins: substance P; neurokinin A; neurokinin B 4. Gastrins: gastrin; cholecystokinins 5. Somatostatins: somatostatin 14; somatostatin 28 6. Glucagon-related: vasoactive intestinal polypeptide 7. Pancreatic-polypeptide 8. Miscellaneous: bombesin; neurotensin; bradykinin; angiotensin; calcitonin gene-related peptide
  • 13.
  • 14. Neurotransmitter receptors They are protein embedded in the plasma membrane of postsynaptic cells Domains of receptor molecules extend into the synaptic cleft bind neurotransmitters This will directly or indirectly cause ion channels in the post synaptic membrane to open or close Resulting ion fluxes will change the membrane potential of post synaptic cell and thus mediating the transfer of information across the synapse.
  • 15. Neurotransmitter Receptors Two main families: A. Ionotropic receptors ligand gated ion channels B. Metabotropic receptors coupled to G-protein uses cAMP or IP3 as 2nd messenger
  • 16. Ionotropic receptors Fast acting ligand-gated ion channels It combine transmitter binding and channel function into single entity Multimers made up of at least 4 or 5 individual protein subunits, each of which contributes to the pore of the ion channel
  • 17. Metabotropic Receptor • Slow acting G-proteins coupled receptors
  • 18. • These receptors do not have ion channels as part of their structure; instead, they affect channels by the activation of intermediate molecules called G-proteins • Aks G-protein-coupled receptors • Are monomeric proteins with an extracellular domain that contains a neurotransmitter binding site and an intracellular domain that binds to G-proteins.
  • 19. Thus, G-proteins can be thought of as transducers that couple neurotransmitter binding to the regulation of postsynaptic ion channels
  • 20. Most neurotransmitters can activate multiple receptor subtypes and receptor classes
  • 22. Steps in chemical transmission
  • 23. Removal of neurotransmitters • Diffusion away from the postsynaptic receptors, OR • Reuptake into nerve terminals or surrounding glial cells, OR • Degradation by specific enzymes, OR • Combination of these mechanisms.

Editor's Notes

  1. Greek tropos means to move in response to a stimulus).
  2. Synaptobrevin syntaxin protein play role in exocytosis of vesicles