Manifestation of Novel Social Challenges of the European

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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of

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-4. 1. 2 -08/1/A-2009 -0011

Manifestation of Novel Social Challenges of the European Union in the Teaching Material of

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-4. 1. 2 -08/1/A-2009 -0011 Tímea Berki and Ferenc Boldizsár Signal transduction ION CHANNEL RECEPTORS

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Ion channel receptors 1 Cys-loop receptors: pentameric structure, 4

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Ion channel receptors 1 Cys-loop receptors: pentameric structure, 4 transmembrane (TM) regions/subunit – Acetylcholin (Ach) Nicotinic R – Na+ channel – GABAA, GABAC, Glycine – Cl- channels (inhibitory role in CNS) 2 Glutamate-activated cationic channels: (excitatory role in CNS), tetrameric stucture, 3 TM regions/subunit – eg. i. Glu 3 ATP-gated channels: 3 homologous subunits, 2 TM regions/subunit – eg. P 2 X purinoreceptor

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Cys-loop ion-channel receptors Pore N N C N TM

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Cys-loop ion-channel receptors Pore N N C N TM 1 Receptor type TM 2 TM 3 TM 4 GABAA a Subunit diversity b GABAC g a 1 -6, b 1 -3, g 1 -3, d, e, k, and q p 2 p 1 -3 Glycine b a a 1 -4, b C C C N

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Vertebrate anionic Cys-loop receptors Type GABAA Glycine (Gly. R)

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Vertebrate anionic Cys-loop receptors Type GABAA Glycine (Gly. R) Class Protein name Gene Previous names alpha a 1 a 2 a 3 a 4 a 5 a 6 GABRA 1 GABRA 2 GABRA 3 GABRA 4 GABRA 5 GABRA 6 beta b 1 b 2 b 3 GABRB 1 GABRB 2 GABRB 3 ECA 5 gamma g 1 g 2 g 3 GABRG 1 GABRG 2 GABRG 3 CAE 2, ECA 2, GEFSP 3 delta d GABRD epsilon e GABRE pi p GABRP theta q GABRQ rho r GABRR GABAC alpha a 1 a 2 a 3 a 4 GLRA 1 GLRA 2 GLRA 3 GLRA 4 STHE beta b GLRB EJM, ECA 4

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Vertebrate cationic Cys-loop receptors Type Serotonin (5 -HT) Class

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Vertebrate cationic Cys-loop receptors Type Serotonin (5 -HT) Class Protein name Gene 5 -HT 3 A 5 -HT 3 B 5 -HT 3 C 5 -HT 3 D 5 -HT 3 E HTR 3 A HTR 3 B HTR 3 C HTR 3 D HTR 3 E alpha a 1 a 2 a 3 a 4 a 5 a 6 a 7 a 8 a 9 a 10 CHRNA 1 CHRNA 2 CHRNA 3 CHRNA 4 CHRNA 5 CHRNA 6 CHRNA 7 CHRNA 8 CHRNA 9 CHRNA 10 ACHRA, ACHRD, CHRNA, CMS 2 A, FCCMS, SCCMS beta b 1 b 2 b 3 b 4 CHRNB 1 CHRNB 2 CHRNB 3 CHRNB 4 CMS 2 A, SCCMS, ACHRB, CHRNB, CMS 1 D, EFNL 3, n. ACh. RB 2 gamma g CHRNG ACHRG delta d CHRND ACHRD, CMS 2 A, FCCMS, SCCMS epsilon e CHRNE ACHRE, CMS 1 D, CMS 1 E, CMS 2 A, FCCMS, SCCMS ZACN ZAC 1, L 2 m, LGICZ 1 5 -HT 3 Nicotinic acetylcholine (n. ACh. R) Zinc-activated ion channel Previous names 5 -HT 3 A 5 -HT 3 B 5 -HT 3 C 5 -HT 3 D 5 -HT 3 E

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Ionotropic glutamate receptors Type AMPA Kainate Class Protein name

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Ionotropic glutamate receptors Type AMPA Kainate Class Protein name Gene Previous names Glu. A 1 Glu. A 2 Glu. A 3 Glu. A 4 GRIA 1 GRIA 2 GRIA 3 GRIA 4 GLUA 1, Glu. RA, Glu. R-K 1, HBGR 1 GLUA 2, Glu. RB, Glu. R-K 2, HBGR 2 GLUA 3, Glu. RC, Glu. R-D, Glu. R-K 3 GLUA 4, Glu. RD, Glu. R-D Glu. K 1 Glu. K 2 Glu. K 3 Glu. K 4 Glu. K 5 GRIK 1 GRIK 2 GRIK 3 GRIK 4 GRI 5 GLUK 5, Glu. R-5, EAA 3 GLUK 6, Glu. R-6, EAA 4, GLUK 7, Glu. R-7, EAA 5, GLUK 1, KA-1, EAA 1 GLUK 2, KA-2, EAA 2 Glu. N 1 NRL 1 A NRL 1 B GRIN 1 GRINL 1 A GRINL 1 B GLUN 1, NMDA-R 1, NR 1, Glu. Rz 1 Glu. N 2 A Glu. N 2 B Glu. N 2 C Glu. N 2 D GRIN 2 A GRIN 2 B GRIN 2 C GRIN 2 D GLUN 2 A, NMDA-R 2 A, NR 2 A, Glu. Re 1 GLUN 2 B, NMDA-R 2 B, NR 2 B, Glu. Re 2 GLUN 2 C, NMDA-R 2 C, NR 2 C, Glu. Re 3 GLUN 2 D, NMDA-R 2 D, NR 2 D, Glu. Re 4 Glu. N 3 A Glu. N 3 B GRIN 3 A GRIN 3 B GLUN 3 A, NMDA-R 3 A, NMDAR-L, chi-1 GLUN 3 B, NMDA-R 3 B Glu. D 1 Glu. D 2 GRID 1 GRID 2 Glu. Rd 1 NMDA ‘Orphan’ (Glu. D)

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Nicotinic Ach receptor • Pore formed from 5 subunits:

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Nicotinic Ach receptor • Pore formed from 5 subunits: 2 a, b, g, d • Opening: the 2 a units are distorted • Desensitization: in the open conformation the b, g, d subunits become phosphorylated by Protein kinase A and C Top Front

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Common neurotransmitters Neurotransmitter Acetylcholine (Ach) Norepinephrine (NE) Action Receptor

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Common neurotransmitters Neurotransmitter Acetylcholine (Ach) Norepinephrine (NE) Action Receptor subtypes +/- Nicotinic, Muscarinic + α 1/2, β 1/2/3 Dopamine +/- D 1 -D 4 Serotonin (5 -HT) +/- 5 -HT 1 A etc. Glutamate (Glu) + NMDA, AMPA GABA - GABAA, GABAB Encephalins - μ, κ, δ

Synapse between two neurons neurotransmission TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Presynaptic neuron (axon terminal)

Synapse between two neurons neurotransmission TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Presynaptic neuron (axon terminal) Synaptic vesicles NT transporter + Neurotransmitter molecule Postsynaptic neuron Voltage-gated sodium channel GPCR (modulatory) Ligand-gated ion channel (direct excitation or inhibition) +

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Neurotransmission Ions Neurotransmitter Plasma membrane Cytoplasm Ion channel Neurotransmitter

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Neurotransmission Ions Neurotransmitter Plasma membrane Cytoplasm Ion channel Neurotransmitter Receptor Plasma membrane Cytoplasm a GTP b g a GTP Effector protein Intracellular messengers G-protein is activated G-protein subunits or intracellular messengers modulate ion channels

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Neurotransmitters Acetylcholine Indolamines Monoamines Catecholamines Amino Acids Acetylcholine (motor

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Neurotransmitters Acetylcholine Indolamines Monoamines Catecholamines Amino Acids Acetylcholine (motor neurons) m/i Serotonin (memory, emotion) m/i Dopamine (motivation, addiction) m Norepinephrine/Noradrenaline (sympathetic NS) m Epinephrine m Glutamate (most prominent in CNS, excitatory) m/i GABA (30%-40% of CNS synapses, inhibitory) m/i i Aspartate Glycine (can be excit. or inhib. depending on Purines Cl - conc. ) * i Adenosine m Guanosine m ATP i/m Others Endorphins Opioids Enkephalins Dynorphins Neuropeptides Substance P Non-opioids Neuropeptide Y Others Soluble gases NO CO m

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Acetylcholine receptors Stage 1 Stage 2 Nicotinic muscle Phenyltrimethyl-ammonium

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Acetylcholine receptors Stage 1 Stage 2 Nicotinic muscle Phenyltrimethyl-ammonium Elapid a-toxins, d-Tubocurarine Stage 3 Nicotinic Junctional [(a 1)2 bed] Nicotinic Embyonic [(a 1)2 bgd] Nicotinic Neuronal a 2 (a-toxin insensitive) Nicotinic Neuronal b 2 Nicotine Nicotinic Neuronal a 3 (a-toxin insensitive) d-Tubocurarine Nicotinic Neuronal b 3 Nicotinic Neuronal a 4 (a-toxin insensitive) Nicotinic neuronal (a+b) Nicotinic Neuronal b 4 Dimethylphenyl-piperazinuim, Cystine Nicotinic Neuronal a 5 (a-toxin insensitive) Trimethaphan Neuronal bungarotoxin Nicotinic Neuronal b 5 Cholinergic Nicotinic Neuronal a 5 (non-functional without a subunits) Acetylcholine Nicotinic Neuronal a 6 (a-toxin insensitive) Nicotinic Neuronal a 7 (a-toxin sensitive) Nicotinic Neuronal a 8 (a-toxin sensitive) Nicotinic Neuronal a 9 Muscarinic m 1 -M 1 Pirenzepine Muscarinic Oxotremorine Muscarine, Pilocarpine Propyllbenzilylcholine mustard Quinuclidinyl benzilate Atropine Muscarinic m 2 -M 2 Methoctramine Muscarinic m 4 -M 4 Himbacine Muscarinic m 3 -M 3 Hexahydro-siladifenidol Muscarinic m 5 -M 5

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Acetylcholin-esterase (Ach. E): • Quick removal of Ach from

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Acetylcholin-esterase (Ach. E): • 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. E