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Neurotransmiters & their Receptors Flashcards

1
Q

Types of receptors

A

Ionotropic and metabotropic

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2
Q

Ligan-gated ion channels

A

ionotropic

  1. neurotransmitter binds
  2. channel opens
  3. ions flow across membrane
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3
Q

g-protein coupled receptors

A

metabotropic

  1. neurotransmitter binds
  2. g-protein is activated
  3. (g-protein subunits or intracellular messengers/effector protein) modulate ion channels
  4. ion channel opens
  5. ions flow across membrane
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4
Q

ionotropic channels

A

ionotropic receptors
fast receptor
intra-molecularly coupled; single protein; binding site and ion channel in single molecule
either depolarization(ESPS, IPSP) or hyperpolarization(IPSP)

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5
Q

metabotropic channels

A

slow
inter-molecularly coupled
activates intracellular messengers that open/close ion channels/ionotropic receptor
* key function: homeostasis and development (gene transcription)

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6
Q

Glutamate

A

ionotropic: AMPA, NMDA, Kainate
metabotropic: Glutamate

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7
Q

GABA

A

ionotropic: GABA
metabotropic: GABA_B

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8
Q

ACh

A

ionotropic: nACh
metabotropic: mACh; muscarinic

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9
Q

Serotonin & Purines

A

also have ionotropic and metabotropic receptors

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10
Q

General architecture of ligand gated receptors ; ionotropic receptors

  1. AMPA
  2. NMDA
  3. Kainate
  4. GABA
  5. Glycine
  6. nACh
  7. Serotonin
  8. Purines
A
  1. AMPA - quadromer
  2. NMDA - pentomer
  3. Kainate - pentomer
  4. GABA - hexomer
  5. Glycine - pentomer
  6. nACh - quadromer
  7. Serotonin - monomer
  8. Purines - 7
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11
Q

nAChR

A

nicotinic Acetyl Choline Receptor
Pentamericprotein
- neuromuscular juction: 2 alpha, beta, gamma, delta
- neuronal ACh: 3 alpha, 2 beta

non-selective cation channels

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12
Q

EPC - end plate current

A

End plate: neuromuscular junction
EPC occurs in both directions based on clamped voltage
1. -100mV (~E_K): Na+ inward current - to depolarize
2. resting membrane potential: Na+ and K+ - to depolarize
3. 0mV: equal net flow
4. +70mV(~E_Na): K+ outward current - to hyperpolarize

  • ions do not move if voltage clamped is close to its equilibrium potential
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13
Q

General architecture of g-protein coupled receptors; metabotropic receptors

Glutamate
GABA_B
Dopamine
NE, Epi
Histamine
Serotonin 
Purines
Muscarinic
A 
Glutamate : ...
GABA_B : dimeric
Dopamine : pentomeric
NE, Epi : pentomeric
Histamine : pentomeric
Serotonin : 7
Purines : ...
Muscarinic : pentomeric
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14
Q

GPCR - G-protein coupled receptor

A

Largest in receptors
5% pf genes in C.elegans
1000 involved in sense of smell

signaling molecules : protein, peptide, amino acid derivatives, fatty acids
* all have the same general structure: span membrane 7 times (serpentine receptor)

N-terminus: extracellular
C-terminus: intracellular - G-protein bound

alter activity of effector proteins/trimeric G-proteins

G-protein bind guanine nucleotides

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15
Q

Trimetric G-protein

A

alpha, beta, gamma subunits
alpha, gamma linked to the membrane covalently
beta and gamma attached and referred as G_bettagamma

Resting state: G_alpha + GDP + G_bettagamma

Receptor activated: binds to G_alpha, GDP released, GTP binds, G_alpha released to bind to active effector, GTP hydrolysis to GDP, back to resting state

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16
Q

Time course of G-protein activation

A

FRET: Fluorescent Resonance Energy Transfer
G_alpha: CFP
G_betta: YFP

CFP light excites YFP when close

cAMP which activates GPCR realse G_alpha from G_bettagamma; reduce in YFP observed

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17
Q

Chimeric protein; adenylyl cyclase

A

to determine which domains of the receptors interact with G-proteins
C3 loop

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18
Q

Cardiac ACh receptors

A

Muscarinic ACh receptor; inhibition
G_alpha_i –> G_alpha is not a regulator
G_bettagamma –> released to activate K+ channel: hyperpolarize; inhibit; make muscles more difficult to contract

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19
Q

Small molecule neurotransmitter

A

Acetylcholine

Amino acid - glutamate, aspartate, GABA, glycine
Purine - ATP
Biogenic amine - catecholamine (dopamine, norepinephrine, epinephrine), indoleamine (serotonin), imidazoleamine (histamine)

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20
Q

Peptide neurotransmitter

A

large density neurotransmitter

21
Q

ACh

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
Acetyl Choline
Excitatory
Choline+acetyl CoA
CAT
AchEase
small clear
22
Q

Glutamate

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
Excitatory
gllutamine
glutaminase
transporters
small clear
23
Q

GABA

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
inhibitory
glutamate
GAD
transporters
small clear
24
Q

Glycine

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
Inhibitory
serine
phosphoserine
transporters
small clear
25
Catecholamine ``` postsynaptic effect precursors rate limiting step in synthesis removal mechanism type of vesicle ```
(epinephrine, norepinephrine, dopamine) ``` excitatory tyrosine tyrosine hydroxylase transporters, MAO, COMT small dense-core, large irregular dense core ```
26
serotonin ``` postsynaptic effect precursors rate limiting step in synthesis removal mechanism type of vesicle ```
``` excitatory tryptophan tryptophan hydroxylase transporters, MAO large, dense-core ```
27
histamine ``` postsynaptic effect precursors rate limiting step in synthesis removal mechanism type of vesicle ```
``` excitatory histidine histidine decarboxylase transporters large, dense-core ```
28
ATP ``` postsynaptic effect precursors rate limiting step in synthesis removal mechanism type of vesicle ```
``` excitatory ADP mitochondrial oxidative phosphorylation; glycolysis hydrolysis to AMPM and adenosine small, clear ```
29
Neuropeptides ``` postsynaptic effect precursors rate limiting step in synthesis removal mechanism type of vesicle ```
``` excitatory and inhibitory amino acids synthesis and transport proteases large, dense-core ```
30
endocannabinoids ``` postsynaptic effect precursors rate limiting step in synthesis removal mechanism type of vesicle ```
``` inhibits inhibition membrane lipids enzymatic modification of lipids hydrolysis by FAAH no vesicle ```
31
Nitric oxide ``` postsynaptic effect precursors rate limiting step in synthesis removal mechanism type of vesicle ```
``` excitatory and inhibitory arginine nitric oxide synthase spontaneous oxidation no vesicle ```
32
Acetylcholine metabolism in cholinergic nerve terminals
(mitochondria) glucose -> pyruvate -> acetyl CoA (choline acetyl tranferase) acetyl CoA + Choline -> acetylcholine (Vesicular ACh transporter) acetylcholine into vesicles (synaptic cleft, acetylcholinersterase) acetylcholine -> acetate + Chooline (Na+/choline symport;transporter) bring choline into the terminal to recycle * Sarin - organophosphates : prevent breakdown of ACh resulting in paralysis
33
Myasthenia Gravis
results from decreased number of nAChRs produce antibody to block activity of nAChRs - lose muscle coordination MEPP amplitude also decreases as lacking nAChRs autoimmune disease treatment: cholinesterase inhibitor; keep profound number of ACh available
34
Glutamate
major excitatory neurotransmitter in CNS | ionotropic (NMDA, AMPA, Kainate) and metabotropic
35
NMDA
``` signal integration synaptic plasticity agonist - N-methyl-D-aspartate (NMDA) neurotransmitter: glutamate Mg2+ blocks during rest - requires glutamate and depolarization to relieve the block slower and longer than AMPA ```
36
AMPA
``` synaptic transmission synaptic plasticity agonist - alpha-amino-3hydroxyl-5-methyl-40isoxazole-proprionate neurotransmitter: glutamate faster and shorter than NMDA ```
37
Kainate
synaptic transmission presynaptic modulation agonist - kainic acid neurotransmitter: glutamate
38
glutamate synthesisand cycling between neurons and glia
(glutaminase) glutamine->glutamate (VGLUT; vesicular glutamate transporter) bring glutamate into vesicles (synaptic cleft, EAAT; excitatory amino acid transporter) bring glutamate into terminal or glia (glutamine synthetase) glutamate->glutamine
39
glutamate induced excitotoxicity
excessive activation of glutamate receptors neuron death post-synaptic cells; dendrites ischemia (caused by stroke); increased glutamate in synapse after injury - decreased function of EAAT & too much Ca2+ in cell
40
Proteolytic processing of the pre-propeptides
pre-propeptide propeptide active peptides
41
neuropeptides
3-36 amino acids shortest: 3; thyrotropin releasing hormone (TRH) longest: 36; Neuropeptide Y
42
ionotropic GABA receptors
Cl- selective channels * other sites are allosteric for GABA binding reversal potential for Cl- is usually lower than resting membrane potential --> usually inhibitory
43
synthesis, release, reuptake of inhibitory neurotransmitter, GABA
(mitochondria) Glucose->Glutamate (glutamic acid decarboxylase & pyridoxal phosphate) glutamate->GABA (VIATT)bring GABA into vesicles (GAT, synaptic cleft) bring GABA into glial cell or terminal
44
endocannabinoid - inhibit inhibition
endougenous signaling molecules synthetic THC - WIN 55,212 act as CB agonist rimonabant act as antagonist lipid precursors inhibit GABAergic function - control GABA release increased Ca2+ in post synaptic cell-> endoC production -> release from the cells -> diffuse back to presynapticcell through CB1 GPCR-> reduced release of GABA from nerve terminal * voltage-gate Ca2+ channels or K+ channels blocked by antagonizing CB1 receptors
45
GABA as an excitatory NT during development
E_Cl -50mV in developing brain, -70mV in adult brain - cf>-68mV resting membrane potential Na+/K+/Cl- co-transporter is highly expressed in immature neuron -> higher intracellular concentration of Cl- K+/Cl- co-transporter as maturation -> pump out Cl-; lowering intracellular concentration
46
Synaptogamin
red | interneurons labeled with MAP2 is green
47
Glutamatergic synapse
``` depolarization NMDA and AMPA nonselective reversal potential near 0mV EPSP generated ```
48
inhibitory synapse
GABAergic synapse E_Cl typically -70mV (mature) if E_Cl is above -50mV (immature), evoke depolarization; yet not enough to evoke AP; IPSP
49
Summation of postsynaptic potential
``` neurotransmitter release receptor binding ion channels open or close conductance change causes current flow postsynaptic potential changes postsynaptic cells excited or inhibited summation determines whether or not an action potential occurs ```

Neurobiology (11 decks)

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