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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
14
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
16
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
20
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