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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University.

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Presentation on theme: "Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University."— Presentation transcript:

1 Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP /1/A

2 ION CHANNEL RECEPTORS Tímea Berki and Ferenc Boldizsár Signal transduction Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP /1/A

3 TÁMOP /1/A Ion channel receptors 1 1Cys-loop receptors: pentameric structure, 4 transmembrane (TM) regions/subunit –Acetylcholin (Ach) Nicotinic R – Na + channel –GABA A, GABA C, Glycine – Cl - channels (inhibitory role in CNS) 2 2Glutamate-activated cationic channels: (excitatory role in CNS), tetrameric stucture, 3 TM regions/subunit –eg. iGlu 3 3ATP-gated channels: 3 homologous subunits, 2 TM regions/subunit –eg. P2X purinoreceptor

4 TÁMOP /1/A Cys-loop ion-channel receptors    p1p2 Receptor type Subunit diversity ,  and  p1-3  GABA A GABA C Glycine TM 1 TM 2 TM 3 TM 4 N C N C N C N C N C Pore

5 TÁMOP /1/A Vertebrate anionic Cys-loop receptors TypeClassProtein nameGenePrevious names GABA A alpha 123456123456 GABRA1 GABRA2 GABRA3 GABRA4 GABRA5 GABRA6 EJM, ECA4 beta 123123 GABRB1 GABRB2 GABRB3 ECA5 gamma 123123 GABRG1 GABRG2 GABRG3 CAE2, ECA2, GEFSP3 delta  GABRD epsilon  GABRE pi  GABRP theta  GABRQ rho  GABRR GABA C Glycine (GlyR) alpha 12341234 GLRA1 GLRA2 GLRA3 GLRA4 STHE beta  GLRB

6 TÁMOP /1/A Vertebrate cationic Cys- loop receptors TypeClassProtein nameGenePrevious names Serotonin (5-HT) 5-HT3 5-HT3A 5-HT3B 5-HT3C 5-HT3D 5-HT3E HTR3A HTR3B HTR3C HTR3D HTR3E 5-HT 3A 5-HT 3B 5-HT 3C 5-HT 3D 5-HT 3E Nicotinic acetylcholine (nAChR) alpha  1  2  3        CHRNA1 CHRNA2 CHRNA3 CHRNA4 CHRNA5 CHRNA6 CHRNA7 CHRNA8 CHRNA9 CHRNA10 ACHRA, ACHRD, CHRNA, CMS2A, FCCMS, SCCMS beta  1  2  3  CHRNB1 CHRNB2 CHRNB3 CHRNB4 CMS2A, SCCMS, ACHRB, CHRNB, CMS1D, EFNL3, nAChRB2 gamma  CHRNGACHRG delta  CHRNDACHRD, CMS2A, FCCMS, SCCMS epsilon  CHRNEACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS Zinc-activated ion channel ZACZACNZAC1, L2m, LGICZ1

7 TÁMOP /1/A Ionotropic glutamate receptors TypeClassProtein nameGenePrevious names AMPAGluA1 GluA2 GluA3 GluA4 GRIA1 GRIA2 GRIA3 GRIA4 GLU A1, GluR1, GluRA, GluR-A, GluR-K1, HBGR1 GLU A2, GluR2, GluRB, GluR-B, GluR-K2, HBGR2 GLU A3, GluR3, GluRC, GluR-D, GluR-K3 GLU A4, GluR4, GluRD, GluR-D KainateGluK GluK1 GluK2 GluK3 GluK4 GluK5 GRIK1 GRIK2 GRIK3 GRIK4 GRI5 GLUK5, GluR5, GluR-5, EAA3 GLUK6, GluR6, GluR-6, EAA4, GLUK7, GluR7, GluR-7, EAA5, GLU K1, KA1, KA-1, EAA1 GLU K2, KA2, KA-2, EAA2 NMDA GluN Glu   L   L  GRIN1 GRINL1A GRINL1B GLU N1, NMDA-R1, NR1, GluR  1 GluN2A GluN2B GluN2C GluN2D GRIN2A GRIN2B GRIN2C GRIN2D GLU N2A, NMDA-R2A, NR2A, GluR  1 GLU N2B, NMDA-R2B, NR2B, GluR  2 GLU N2C, NMDA-R2C, NR2C, GluR  3 GLU N2D, NMDA-R2D, NR2D, GluR  4 GluN3A GluN3B GRIN3A GRIN3B GLU N3A, NMDA-R3A, NMDAR-L, chi-1 GLU N3B, NMDA-R3B ‘Orphan’(GluD) GluD1 GluD2 GRID1 GRID2 GluR  1

8 TÁMOP /1/A Nicotinic Ach receptor Pore formed from 5 subunits: 2 , , ,  Opening: the 2  units are distorted Desensitization: in the open conformation the , ,  subunits become phosphorylated by Protein kinase A and C TopFront

9 TÁMOP /1/A Common neurotransmitters NeurotransmitterActionReceptor subtypes Acetylcholine (Ach)+/-Nicotinic, Muscarinic Norepinephrine (NE)+α1/2, β1/2/3 Dopamine+/-D1-D4 Serotonin (5-HT)+/-5-HT1 A etc. Glutamate (Glu)+NMDA, AMPA GABA-GABA A, GABA B Encephalins-μ, κ, δ

10 TÁMOP /1/A Presynaptic neuron (axon terminal) Postsynaptic neuron Neurotransmitter molecule NT transporter Synaptic vesicles Voltage- gated sodium channel GPCR (modulator y) Ligand- gated ion channel (direct excitation or inhibition) + + Synapse between two neurons - neurotransmission

11 TÁMOP /1/A Neurotransmission Ions GTP  Receptor G-protein is activated Effector protein Intracellular messengers G-protein subunits or intracellular messengers modulate ion channels Neurotransmitter GTP    Cytoplasm Plasma membrane Neurotransmitter Ion channel Cytoplasm Plasma membrane

12 TÁMOP /1/A NeurotransmittersAcetylcholineAcetylcholine MonoaminesMonoamines Amino Acids PurinesPurines NeuropeptidesNeuropeptides Soluble gases IndolaminesIndolamines CatecholaminesCatecholamines OpioidsOpioids Non-opioidsNon-opioids Endorphins Enkephalins Dynorphins NO CO Acetylcholine (motor neurons) Serotonin (memory, emotion) m/i m/i Dopamine (motivation, addiction) Norepinephrine/Noradrenaline (sympathetic NS) Epinephrine m m m Glutamate (most prominent in CNS, excitatory) GABA (30%-40% of CNS synapses, inhibitory) Aspartate Glycine (can be excit. or inhib. depending on Cl - conc.) * i m/i m/i i Adenosine Guanosine ATP Others i/m m m Substance P Neuropeptide Y Others m

13 TÁMOP /1/A Acetylcholine receptors Nicotinic Neuronal a2 (a-toxin insensitive) Nicotinic Neuronal a3 (a-toxin insensitive) Nicotinic Neuronal a4 (a-toxin insensitive) Nicotinic Neuronal a5 (a-toxin insensitive) Nicotinic Neuronal a5 (non-functional without a subunits) Nicotinic Neuronal a6 (a-toxin insensitive) Nicotinic Neuronal a7 (a-toxin sensitive) Nicotinic Neuronal a8 (a-toxin sensitive) Nicotinic Neuronal a9 Nicotinic Neuronal b2 Nicotinic Neuronal b3 Nicotinic Neuronal b4 Nicotinic Neuronal b5 Nicotinic muscle Phenyltrimethyl-ammonium Elapid a-toxins, d-Tubocurarine Nicotinic Junctional [(a1) 2 bed] Nicotinic Embyonic [(a1) 2 bgd] Nicotinic neuronal (a+b) Dimethylphenyl-piperazinuim, Cystine Trimethaphan Neuronal bungarotoxin Oxotremorine Propyllbenzilylcholine mustard Quinuclidinyl benzilate Muscarinic m 5 -M 5 Muscarinic m 1 -M 1 Pirenzepine Muscarinic m 2 -M 2 Methoctramine Muscarinic m 3 -M 3 Hexahydro-siladifenidol Muscarinic m 4 -M 4 Himbacine Nicotinic Nicotine d-Tubocurarine Muscarinic Muscarine, Pilocarpine Atropine Stage 1 Stage 2 Stage 3

14 TÁMOP /1/A Acetylcholin-esterase (AchE): Quick removal of Ach from the synaptic space Ach → choline+acetyl Reversible inhibitors: therapeutic use (myasthenia, glaucoma, Alzheimer’s) Irreversible inhibitors: chemical weapons and pesticides eg. organophosphates Ach AchE


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