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Neurobiology > Neurotransmiters & their Receptors > Flashcards

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
Q

Catecholamine

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A

(epinephrine, norepinephrine, dopamine)

excitatory
tyrosine
tyrosine hydroxylase
transporters, MAO, COMT
small dense-core, large irregular dense core
26
Q

serotonin

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
excitatory
tryptophan
tryptophan hydroxylase
transporters, MAO
large, dense-core
27
Q

histamine

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
excitatory
histidine
histidine decarboxylase
transporters
large, dense-core
28
Q

ATP

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
excitatory
ADP
mitochondrial oxidative phosphorylation; glycolysis
hydrolysis to AMPM and adenosine
small, clear
29
Q

Neuropeptides

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
excitatory and inhibitory
amino acids
synthesis and transport
proteases
large, dense-core
30
Q

endocannabinoids

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
inhibits inhibition
membrane lipids
enzymatic modification of lipids
hydrolysis by FAAH
no vesicle
31
Q

Nitric oxide

postsynaptic effect
precursors
rate limiting step in synthesis
removal mechanism
type of vesicle
A 
excitatory and inhibitory
arginine
nitric oxide synthase
spontaneous oxidation
no vesicle
32
Q

Acetylcholine metabolism in cholinergic nerve terminals

A

(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
Q

Myasthenia Gravis

A

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
Q

Glutamate

A

major excitatory neurotransmitter in CNS

ionotropic (NMDA, AMPA, Kainate) and metabotropic

35
Q

NMDA

A 
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
Q

AMPA

A 
synaptic transmission
synaptic plasticity
agonist - alpha-amino-3hydroxyl-5-methyl-40isoxazole-proprionate
neurotransmitter: glutamate
faster and shorter than NMDA
37
Q

Kainate

A

synaptic transmission
presynaptic modulation
agonist - kainic acid
neurotransmitter: glutamate

38
Q

glutamate synthesisand cycling between neurons and glia

A

(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
Q

glutamate induced excitotoxicity

A

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
Q

Proteolytic processing of the pre-propeptides

A

pre-propeptide
propeptide
active peptides

41
Q

neuropeptides

A

3-36 amino acids

shortest: 3; thyrotropin releasing hormone (TRH)
longest: 36; Neuropeptide Y

42
Q

ionotropic GABA receptors

A

Cl- selective channels
* other sites are allosteric for GABA binding
reversal potential for Cl- is usually lower than resting membrane potential –> usually inhibitory

43
Q

synthesis, release, reuptake of inhibitory neurotransmitter, GABA

A

(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
Q

endocannabinoid - inhibit inhibition

A

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
Q

GABA as an excitatory NT during development

A

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
Q

Synaptogamin

A

red

interneurons labeled with MAP2 is green

47
Q

Glutamatergic synapse

A 
depolarization
NMDA and AMPA
nonselective
reversal potential near 0mV
EPSP generated
48
Q

inhibitory synapse

A

GABAergic synapse
E_Cl typically -70mV (mature)
if E_Cl is above -50mV (immature), evoke depolarization; yet not enough to evoke AP; IPSP

49
Q

Summation of postsynaptic potential

A 
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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