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Neurotransmitters & Receptors

Neurotransmitters & Receptors. Sensory neuron Motor neuron Receptor potentialAction potential Synaptic potential Action potential

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Neurotransmitters & Receptors

Sensory neuronMotor neuronReceptor potentialAction potentialSynaptic potentialAction potential2

Excitatory Post-Synaptic Potential (EPSP)

Removal of neurotransmitter from the synapseReuptakeEnzymatic deactivationDiffusion4Neurotransmitter binds to postsynaptic receptorsand can Influence neurotransmitter-dependent channels:1) Direct2) Indirect

neurotransmitter-dependent channels2. Metabotropic Receptors1. Ionotropic Receptor

6neurotransmitter-dependent channels

2. Metabotropic Receptors1. Ionotropic receptorIn all cases, the neurotransmitter does not pass from one neuron to another7Ionotropic MetabotropicFast effectOnly opens transmitter dependent channels Slow effectmay open/close transmitter dependent channels8NeurotransmittersWho is a neurotransmitter?Four criteria:Synthesis in the neuronPresent in pre-synaptic terminals and released in a sufficient amount to influence a post-synaptic neuron/organWhen administered exogenously (drug) mimics the effect of the endogenously neurotransmitterA specific removal mechanism exists10Neurotransmitter: fast and local in the synapseNeuromodulator: more diffuse and modulating effectNeurohormones: through the blood stream distant targets11NeurotransmittersTwo basic effects:EPSPIPSPThe receptor, NOT neurotransmitter, determines whether the post-synaptic effect of a neurotransmitter will be:Inhibitory or excitatoryDirect or indirect12Two basic effects:EPSP: GlutamateIPSP: GABA (gamma-aminobutyric acid), GlycineNeurotransmitters13EPSP Glutamate Glutamate Ionotropic receptors:

N-methylD-aspartate (NMDA receptor) non-selective for cations and opens Na+, K+, and Ca2+ channels

-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor) Na+ & K+

Kainate receptor

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NMDAA Neurotransmitter and Voltage dependent channelNeurotransmitter dependent: Glutamate + Glycine open the channel voltage dependent: Depolarization Mg2+ is removed Channel open late effect

Involved in synaptic plasticity, learning & memoryPCP: Does not normally block the channel15Two types of receptors:GABAa - Ionotropic receptor that opens Cl- channels (fast) GABAb - metabotropic receptor that opens K+ channels (slow) GABAIPSP

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GABAaNeurotransmitter dependent Cl- channelMuscimol direct agonistBicuculline direct antagonist17But we have more than just two types of neurotransmittersAcetylcholineMonoaminesCatecholaminesEpinephrineNorepinephrineDopamineIndolaminesSerotoninPeptidesex. opiods

18AcetylcholineMuscular movementMotor neuron muscle synapse.Also in central nervous systemImportant for learning/memoryTreatment for AlzheimerIn peripheral nervous systemAutonomic nervous system 19AcetylcholineTwo types of receptors:Nicotinic ionotropic Na+ & K+ (and some Ca2+) 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 removalRemoval mechanism AchE breaks Ach apart 21Another group of neurotransmitters are the Monoamines:

Epinephrine

Norepinephrine

Dopamine

SerotoninModulate information processing: Very few neurons but great divergence Metabotropic receptors slow effectDopamineNorepinephrineTyrosineL-DopaDopamineNorepinephrineDopamine Beta-hydroxylase23DopamineMovement, attention, learning, motivationBoth inhibitory and excitatoryDepending on the receptorAll metabotropic (D1, D2, ..)Parkinsons Disease low dopamine(using L-Dopa can increase dopamine levels)24NorepinephrineAlertness and vigilanceBoth inhibitory and excitatoryBut behavioral effect is usually excitatory25SerotoninAt least 14 different receptors (5HT1,5HT2..)5HT3 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)

tryptophan5-HTP5-HT26How 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)

#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 Chemicals that mimic the function of a neurotransmitter are called:

Agonists

Chemicals that disrupt the function of a neurotransmitter are called:

Antagonists