Neurotransmitters 1
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Neurotransmitters are endogenous chemicals that transmit signals between neurons. They are packaged into synaptic vesicles and released from the presynaptic neuron in response to an action potential. Neurotransmitters bind to receptors on the postsynaptic neuron, causing ion channels to open or close and changing the membrane potential. The main neurotransmitters are acetylcholine, dopamine, norepinephrine, epinephrine, GABA, serotonin, nitric oxide, and neuropeptides. Neurotransmitters are removed from the synapse through diffusion, reuptake, or enzymatic degradation.
Neurotransmitters 1
- 1. Neurotransmitters Dr. Surakshya Gautam Department of Biochemistry
- 2. Objectives Neurotransmitters : Definition, properties Synaptic transmission Neuromuscular transmission Neurotransmitter receptors Types : Acetyl choline, Dopamine, NE, E, GABA, Serotonin, NO
- 4. Synaptic transmission Synaptic cleft Synaptic vesicles Neurotransmitter Around 10,000 molecules of NT are contained in vesicle
- 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
- 12. Specific to ion
- 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.