Download - Ion channel receptors
Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
ION CHANNEL RECEPTORS
Tímea Berki and Ferenc BoldizsárSignal transduction
Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
TÁMOP-4.1.2-08/1/A-2009-0011
Ion channel receptors1 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. iGlu
3 ATP-gated channels: 3 homologous subunits, 2 TM regions/subunit– eg. P2X purinoreceptor
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Cys-loop ion-channel receptors
a bg
abp1p2
Receptor type
Subunit diversity a1-6, b1-3, g1-3, d,e,k, and q p1-3 a1-4, b
GABAA GABAC Glycine
TM1
TM2
TM3
TM4
N
CN
CN
C
NCNC
Pore
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Vertebrate anionic Cys-loop receptors
Type Class Protein name Gene Previous names
GABAA
alpha
a1a2a3a4a5a6
GABRA1GABRA2GABRA3GABRA4GABRA5GABRA6
EJM, ECA4
betab1b2b3
GABRB1GABRB2GABRB3
ECA5
gammag1g2g3
GABRG1GABRG2GABRG3
CAE2, ECA2, GEFSP3
delta d GABRD
epsilon e GABRE
pi p GABRP
theta q GABRQ
rho rGABRRGABRRGABRR
GABAC
Glycine (GlyR)alpha
a1a2a3a4
GLRA1GLRA2GLRA3GLRA4
STHE
beta b GLRB
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Vertebrate cationic Cys-loop receptors
Type Class Protein name Gene Previous names
Serotonin(5-HT)
5-HT3
5-HT3A5-HT3B5-HT3C5-HT3D5-HT3E
HTR3AHTR3BHTR3CHTR3DHTR3E
5-HT3A
5-HT3B
5-HT3C
5-HT3D
5-HT3E
Nicotinic acetylcholine(nAChR)
alpha
a1a2a3a4a5a6a7a8a9a10
CHRNA1CHRNA2CHRNA3CHRNA4CHRNA5CHRNA6CHRNA7CHRNA8CHRNA9
CHRNA10
ACHRA, ACHRD, CHRNA, CMS2A, FCCMS, SCCMS
beta
b1b2b3b4
CHRNB1CHRNB2CHRNB3CHRNB4
CMS2A, SCCMS, ACHRB, CHRNB, CMS1D, EFNL3, nAChRB2
gamma g CHRNG ACHRG
delta d CHRND ACHRD, CMS2A, FCCMS, SCCMS
epsilon e CHRNE ACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS
Zinc-activated ion channel
ZAC ZACN ZAC1, L2m, LGICZ1
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Ionotropic glutamate receptors
Type Class Protein name Gene Previous names
AMPA GluA1
GluA1GluA2GluA3GluA4
GRIA1GRIA2GRIA3GRIA4
GLUA1, GluR1, GluRA, GluR-A, GluR-K1, HBGR1GLUA2, GluR2, GluRB, GluR-B, GluR-K2, HBGR2
GLUA3, GluR3, GluRC, GluR-D, GluR-K3GLUA4, GluR4, GluRD, GluR-D
Kainate GluK
GluK1GluK2GluK3GluK4GluK5
GRIK1GRIK2GRIK3GRIK4GRI5
GLUK5, GluR5, GluR-5, EAA3GLUK6, GluR6, GluR-6, EAA4, GLUK7, GluR7, GluR-7, EAA5,
GLUK1, KA1, KA-1, EAA1GLUK2, KA2, KA-2, EAA2
NMDA
GluNGluN1NRL1ANRL1B
GRIN1GRINL1AGRINL1B
GLUN1, NMDA-R1, NR1, GluRz1
GluN2AGluN2BGluN2CGluN2D
GRIN2AGRIN2BGRIN2CGRIN2D
GLUN2A, NMDA-R2A, NR2A, GluRe1GLUN2B, NMDA-R2B, NR2B, GluRe2GLUN2C, NMDA-R2C, NR2C, GluRe3GLUN2D, NMDA-R2D, NR2D, GluRe4
GluN3AGluN3B
GRIN3AGRIN3B
GLUN3A, NMDA-R3A, NMDAR-L, chi-1GLUN3B, NMDA-R3B
‘Orphan’ (GluD)GluD1GluD2
GRID1GRID2
GluRd1
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Nicotinic Ach receptor• Pore formed from 5 subunits: 2a, b, g, d• Opening: the 2a units are distorted • Desensitization: in the open conformation the b, g, d
subunits become phosphorylated by Protein kinase A and C
Top Front
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Common neurotransmitters
Neurotransmitter Action Receptor subtypes
Acetylcholine (Ach) +/- Nicotinic, Muscarinic
Norepinephrine (NE) + 1/2, 1/2/3α β
Dopamine +/- D1-D4
Serotonin (5-HT) +/- 5-HT1A etc.
Glutamate (Glu) + NMDA, AMPA
GABA - GABAA, GABAB
Encephalins - , , μ κ δ
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Presynaptic neuron(axon terminal)
Postsynaptic neuron
Neurotransmitter molecule
NT transporter
Synaptic vesicles
Voltage-gated sodium channel
GPCR (modulatory
)
Ligand-gated ion channel
(direct excitation or inhibition)
+
+
Synapse between two neurons - neurotransmission
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NeurotransmissionIons
GTP
a
Receptor
G-protein isactivated
Effector protein
Intracellularmessengers
G-protein subunits or intracellularmessengers modulate ion channels
Neurotransmitter
GTP
gba
Cytoplasm
Plasma membrane
Neurotransmitter
Ion channel
Cytoplasm
Plasma membrane
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NeurotransmittersAcetylcholine
Monoamines
Amino Acids
Purines
Neuropeptides
Soluble gases
Indolamines
Catecholamines
Opioids
Non-opioids
EndorphinsEnkephalinsDynorphins
NOCO
Acetylcholine (motor neurons)
Serotonin (memory, emotion)
m/i
m/i
Dopamine (motivation, addiction)Norepinephrine/Noradrenaline (sympathetic NS)Epinephrine
mmm
Glutamate (most prominent in CNS, excitatory)GABA (30%-40% of CNS synapses, inhibitory)AspartateGlycine (can be excit. or inhib. depending on Cl- conc.) *i
m/im/ii
AdenosineGuanosineATPOthers
i/mmm
Substance PNeuropeptide YOthers
m
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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 musclePhenyltrimethyl-ammoniumElapid a-toxins, d-Tubocurarine
Nicotinic Junctional [(a1)2bed]
Nicotinic Embyonic [(a1)2bgd]
Nicotinic neuronal (a+b)Dimethylphenyl-piperazinuim,CystineTrimethaphanNeuronal bungarotoxin
OxotremorinePropyllbenzilylcholine mustardQuinuclidinyl benzilate
Muscarinic m5-M5
Muscarinic m1-M1Pirenzepine
Muscarinic m2-M2Methoctramine
Muscarinic m3-M3Hexahydro-siladifenidol
Muscarinic m4-M4Himbacine
NicotinicNicotined-Tubocurarine
MuscarinicMuscarine, PilocarpineAtropine
CholinergicAcetylcholine
Stage 1 Stage 2 Stage 3
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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. organophosphatesAch
AchE