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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s P rogrammes at the University of Pécs and at the University of Debrecen Identification number : TÁMOP-4.1.2-08/1/A-2009-0011. - PowerPoint PPT Presentation

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Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Masters Programmesat the University of Pcs and at the University of DebrecenIdentification number: TMOP-4.1.2-08/1/A-2009-0011Ion channel receptorsTmea Berki and Ferenc BoldizsrSignal transductionManifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Masters Programmesat the University of Pcs and at the University of DebrecenIdentification number: TMOP-4.1.2-08/1/A-2009-0011Ion channel receptors1Cys-loop receptors: pentameric structure, 4 transmembrane (TM) regions/subunitAcetylcholin (Ach) Nicotinic R Na+ channelGABAA, GABAC, Glycine Cl- channels (inhibitory role in CNS) 2Glutamate-activated cationic channels: (excitatory role in CNS), tetrameric stucture, 3 TM regions/subuniteg. iGlu 3ATP-gated channels: 3 homologous subunits, 2 TM regions/subuniteg. P2X purinoreceptor

TMOP-4.1.2-08/1/A-2009-0011Cys-loop ion-channel receptorsabgabp1p2Receptor typeSubunit diversitya1-6, b1-3, g1-3, d,e,k, and qp1-3a1-4, bGABAAGABACGlycineTM1TM2TM3TM4NCNCNCNCNCPoreTMOP-4.1.2-08/1/A-2009-0011Vertebrate anionic Cys-loop receptorsTypeClassProtein nameGenePrevious namesGABAAalphaa1a2a3a4a5a6GABRA1GABRA2GABRA3GABRA4GABRA5GABRA6EJM, ECA4

betab1b2b3GABRB1GABRB2GABRB3ECA5gammag1g2g3GABRG1GABRG2GABRG3CAE2, ECA2, GEFSP3deltadGABRDepsiloneGABREpipGABRPthetaqGABRQrhorGABRRGABRRGABRRGABACGlycine (GlyR)alphaa1a2a3a4GLRA1GLRA2GLRA3GLRA4STHEbetabGLRBTMOP-4.1.2-08/1/A-2009-0011Vertebrate cationic Cys-loop receptorsTypeClassProtein nameGenePrevious namesSerotonin(5-HT)5-HT35-HT3A5-HT3B5-HT3C5-HT3D5-HT3E

HTR3AHTR3BHTR3CHTR3DHTR3E

5-HT3A5-HT3B5-HT3C5-HT3D5-HT3ENicotinic acetylcholine(nAChR)alphaa1a2a3a4a5a6a7a8a9a10CHRNA1CHRNA2CHRNA3CHRNA4CHRNA5CHRNA6CHRNA7CHRNA8CHRNA9CHRNA10ACHRA, ACHRD, CHRNA, CMS2A, FCCMS, SCCMSbetab1b2b3b4CHRNB1CHRNB2CHRNB3CHRNB4CMS2A, SCCMS, ACHRB, CHRNB, CMS1D, EFNL3, nAChRB2gammagCHRNGACHRGdeltadCHRNDACHRD, CMS2A, FCCMS, SCCMSepsiloneCHRNEACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMSZinc-activated ion channelZACZACNZAC1, L2m, LGICZ1TMOP-4.1.2-08/1/A-2009-0011Ionotropic glutamate receptorsTypeClassProtein nameGenePrevious namesAMPAGluA1GluA1GluA2GluA3GluA4GRIA1GRIA2GRIA3GRIA4GLUA1, GluR1, GluRA, GluR-A, GluR-K1, HBGR1GLUA2, GluR2, GluRB, GluR-B, GluR-K2, HBGR2GLUA3, GluR3, GluRC, GluR-D, GluR-K3GLUA4, GluR4, GluRD, GluR-DKainateGluKGluK1GluK2GluK3GluK4GluK5GRIK1GRIK2GRIK3GRIK4GRI5GLUK5, GluR5, GluR-5, EAA3GLUK6, GluR6, GluR-6, EAA4, GLUK7, GluR7, GluR-7, EAA5, GLUK1, KA1, KA-1, EAA1GLUK2, KA2, KA-2, EAA2NMDAGluNGluN1NRL1ANRL1BGRIN1GRINL1AGRINL1BGLUN1, NMDA-R1, NR1, GluRz1GluN2AGluN2BGluN2CGluN2DGRIN2AGRIN2BGRIN2CGRIN2DGLUN2A, NMDA-R2A, NR2A, GluRe1GLUN2B, NMDA-R2B, NR2B, GluRe2GLUN2C, NMDA-R2C, NR2C, GluRe3GLUN2D, NMDA-R2D, NR2D, GluRe4GluN3AGluN3BGRIN3AGRIN3BGLUN3A, NMDA-R3A, NMDAR-L, chi-1GLUN3B, NMDA-R3BOrphan(GluD)GluD1GluD2GRID1GRID2GluRd1TMOP-4.1.2-08/1/A-2009-0011Nicotinic Ach receptorPore formed from 5 subunits: 2a, b, g, dOpening: the 2a units are distorted Desensitization: in the open conformation the b, g, d subunits become phosphorylated by Protein kinase A and C

TopFrontTMOP-4.1.2-08/1/A-2009-0011Common neurotransmittersNeurotransmitterActionReceptor subtypesAcetylcholine (Ach)+/-Nicotinic, MuscarinicNorepinephrine (NE)+1/2, 1/2/3Dopamine+/-D1-D4Serotonin (5-HT)+/-5-HT1A etc.Glutamate (Glu)+NMDA, AMPAGABA-GABAA, GABABEncephalins-, , TMOP-4.1.2-08/1/A-2009-0011Presynaptic neuron(axon terminal)Postsynaptic neuronNeurotransmitter moleculeNT transporterSynaptic vesiclesVoltage-gated sodium channelGPCR (modulatory)Ligand-gated ion channel(direct excitation or inhibition)++Synapse between two neurons - neurotransmissionTMOP-4.1.2-08/1/A-2009-001110NeurotransmissionIonsGTPaReceptor G-protein isactivatedEffector proteinIntracellularmessengersG-protein subunits or intracellularmessengers modulate ion channelsNeurotransmitterGTPgbaCytoplasmPlasma membraneNeurotransmitterIon channelCytoplasmPlasma membraneTMOP-4.1.2-08/1/A-2009-0011NeurotransmittersAcetylcholineMonoaminesAmino AcidsPurinesNeuropeptidesSoluble gasesIndolaminesCatecholaminesOpioidsNon-opioidsEndorphinsEnkephalinsDynorphinsNOCOAcetylcholine (motor neurons)Serotonin (memory, emotion)m/im/iDopamine (motivation, addiction)Norepinephrine/Noradrenaline (sympathetic NS)EpinephrinemmmGlutamate (most prominent in CNS, excitatory)GABA (30%-40% of CNS synapses, inhibitory)AspartateGlycine (can be excit. or inhib. depending on Cl- conc.) *im/im/iiAdenosineGuanosineATPOthersi/mmmSubstance PNeuropeptide YOthersmTMOP-4.1.2-08/1/A-2009-0011Acetylcholine receptorsNicotinic 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 a9Nicotinic Neuronal b2Nicotinic Neuronal b3Nicotinic Neuronal b4Nicotinic Neuronal b5Nicotinic musclePhenyltrimethyl-ammoniumElapid a-toxins, d-TubocurarineNicotinic Junctional [(a1)2bed]Nicotinic Embyonic [(a1)2bgd]Nicotinic neuronal (a+b)Dimethylphenyl-piperazinuim,CystineTrimethaphanNeuronal bungarotoxinOxotremorinePropyllbenzilylcholine mustardQuinuclidinyl benzilateMuscarinic m5-M5Muscarinic m1-M1PirenzepineMuscarinic m2-M2MethoctramineMuscarinic m3-M3Hexahydro-siladifenidolMuscarinic m4-M4HimbacineNicotinicNicotined-TubocurarineMuscarinicMuscarine, PilocarpineAtropineCholinergicAcetylcholineStage 1Stage 2Stage 3TMOP-4.1.2-08/1/A-2009-0011Acetylcholin-esterase (AchE):Quick removal of Ach from the synaptic spaceAch choline+acetylReversible inhibitors: therapeutic use (myasthenia, glaucoma, Alzheimers)Irreversible inhibitors: chemical weapons and pesticides eg. organophosphates

AchAchETMOP-4.1.2-08/1/A-2009-0011

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