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Neurotransmitters & Receptors
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Sensory neuron Motor neuron Receptor potentialAction potential Synaptic potential Action potential
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Excitatory Post-Synaptic Potential (EPSP)
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Removal of neurotransmitter from the synapse 1.Reuptake 2.Enzymatic deactivation 3.Diffusion
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Neurotransmitter binds to postsynaptic receptors and can Influence neurotransmitter-dependent channels: 1) Direct 2) Indirect
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neurotransmitter-dependent channels 2. Metabotropic Receptors 1. Ionotropic Receptor
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neurotransmitter-dependent channels 2. Metabotropic Receptors 1. Ionotropic receptor In all cases, the neurotransmitter does not pass from one neuron to another
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Ionotropic Metabotropic Fast effect Only opens transmitter dependent channels Slow effect may open/close transmitter dependent channels
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Neurotransmitters
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Who is a neurotransmitter? Four criteria: 1.Synthesis in the neuron 2.Present in pre-synaptic terminals and released in a sufficient amount to influence a post-synaptic neuron/organ 3.When administered exogenously (drug)– mimics the effect of the endogenously neurotransmitter 4.A specific removal mechanism exists
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Neurotransmitter: fast and local in the synapse Neuromodulator: more diffuse and modulating effect Neurohormones: through the blood stream – distant targets
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Neurotransmitters Two basic effects: – EPSP – IPSP The receptor, NOT neurotransmitter, determines whether the post-synaptic effect of a neurotransmitter will be: Inhibitory or excitatory Direct or indirect
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Two basic effects: – EPSP: Glutamate – IPSP: GABA (gamma-aminobutyric acid), Glycine Neurotransmitters
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EPSP Glutamate Glutamate Ionotropic receptors: N-methyl D-aspartate (NMDA receptor) – non-selective for cations and opens Na +, K +, and Ca 2+ channels α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor) Na+ & K+ Kainate receptor
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NMDA A Neurotransmitter and Voltage dependent channel Neurotransmitter dependent: Glutamate + Glycine open the channel voltage dependent: Depolarization Mg2+ is removed Channel open – late effect Involved in synaptic plasticity, learning & memory PCP: Does not normally block the channel
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Two types of receptors: GABAa - Ionotropic receptor that opens Cl- channels (fast) GABAb - metabotropic receptor that opens K + channels (slow) GABA IPSP
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GABAa Neurotransmitter dependent Cl- channel Muscimol – direct agonist Bicuculline – direct antagonist
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But we have more than just two types of neurotransmitters Acetylcholine Monoamines – Catecholamines Epinephrine Norepinephrine Dopamine – Indolamines Serotonin Peptides – ex. opiods
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Acetylcholine Muscular movement – Motor neuron – muscle synapse. Also in central nervous system – Important for learning/memory Treatment for Alzheimer In peripheral nervous system – Autonomic nervous system
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Acetylcholine Two types of receptors: – Nicotinic – ionotropic – Na+ & K+ (and some Ca 2+ ) EPSP – Muscarinic – metabotropic – close K+ Slow EPSP easier to generate action potential Name of the receptor – the drugs that activate it
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Reuptake of choline by transporter – for recycling not removal Removal mechanism – AchE – breaks Ach apart
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Another group of neurotransmitters are the Monoamines: Epinephrine Norepinephrine Dopamine Serotonin Modulate information processing: Very few neurons – but great divergence Metabotropic receptors – slow effect
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Dopamine Norepinephrine Tyrosine L-Dopa Dopamine Norepinephrine Dopamine Beta-hydroxylase
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Dopamine Movement, attention, learning, motivation Both inhibitory and excitatory – Depending on the receptor – All metabotropic (D 1, D 2, …..) Parkinson’s Disease – low dopamine (using L-Dopa can increase dopamine levels)
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Norepinephrine Alertness and vigilance Both inhibitory and excitatory – But behavioral effect is usually excitatory
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Serotonin At least 14 different receptors (5HT 1,5HT 2..) – 5HT 3 – ionotropic – Na+ & K+ Low levels of serotonin (due to stress, lack of proper sleep, poor diet/exercise) can lead to irritability, anxiety, fatigue, chronic pain, and even depression – SSRI – Specific Serotonin Reuptake Inhibitors (e.g. Prozac) tryptophan 5-HTP 5-HT
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How can we modulate the effect of neurotransmitters? #1. Precursor (e.g. L-Dopa) #2. Inactivation of an enzyme needed for synthesis (e.g. blocking dopamine beta-hydroxylase) #3 Preventing storage (by inactivating the vesicle transporter)
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#4 Stimulation of release from terminal button #5 Inhibition of release from terminal button #6 Receptor blockers #7 Stimulation of auto-receptors #8 Reuptake #9 Enzymatic deactivation
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Chemicals that mimic the function of a neurotransmitter are called: Agonists Chemicals that disrupt the function of a neurotransmitter are called: Antagonists
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