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Neurotransmitter Systems Part 2 Flashcards

1
Q

What do benzodiazepines (valium) and barbiturates (phenobarbtiol) do?

A

Act on GABA-A and Glycine channels
benzo = inc freq of opening
barbs = inc channel open time

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2
Q

This NT is removed from the synapse by high affinity transporters (GATs) into neurons and glia

A

GABA

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3
Q

This AA NT is broken down in mitochondria

A

GABA

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4
Q

SLIDE 60

A

SLIDE 60

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5
Q

D1-5

A

GPCR

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6
Q

This amino acid NT is packaged into synaptic vesicles by a vesicular inhibitory amino acid transporter (VIAAT)

A

GABA

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7
Q

How are subtypes for transmitter gated channels important in drug development?

A

We need to be able to identify drugs that only work on specific subtypes of the channel to only block the one binding pocket and not the other or only stimulate the one and not the other

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8
Q

How can a GPCR amplify a signal?

A

The ligand binding can impact multiple G proteins which impact multiple pathways which impact multiple cascades and so on (SLIDE 61)

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9
Q

Where do G proteins bind on GPCRs?

A

Some of the intracellular loop

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10
Q

SLIDE 62

A

SLIDE 62

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11
Q

This purine NT is excitatory in sensory and autonomic ganglia in motor neurons

A

ATP

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12
Q

Signaling deficits of this NT are associated with Huntington’s, Parkinson’s, schizo, and senile dementia

A

GABA

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13
Q

This NT is synthesized from serine by serine hydroxymetyltransfrase

A

Glycine

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14
Q

Strychnine is an antagonist of this receptor

A

Glycine receptors

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15
Q

These types of receptors have one ligand gated family (P2X1-P2X7) and two transmembrane domains

A

Purine NT receptors

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16
Q

3 of these subunits labeled 2-4

A

beta

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17
Q

The channel of these glutamate receptors is blocked by Mg at -65 mV (inward current is voltage dependent)

A

NMDA

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18
Q

What do different subunits create in transmitter gated channels and how do those then have an effect on the channel?

A

Subunits create different subtypes which have different affinities for NTs (one subtype may allow binding at a lower concentration, higher concentration, etc)

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19
Q

Two types of this NT include anandamide and 2-arachidonylglycerol (2-AG)

A

Endocannabinoids

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20
Q

This is an endogenous protein that is similar to cobra venom

A

Lynx1 protein

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21
Q

These transmitter gated channels only have 4 subunits

A

Glutamate

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22
Q

These receptors are modulated by benzodiazepines (valium) to inc frequency of opening and barbiturates (phenobarbital) to inc channel open time

A

GABA-A and Glycine channels

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23
Q

These two NTs are used in the synthesis of proteins and thus present in all cells

A

Glutamate and glycine

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24
Q

What can a dietary deficiency of vitamin B6 lead to?

A

Lower levels of GABA synthesis which can lead to seizures

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25
Q

A G protein coupled system that involves multiple steps and the activation of enzymes

A

Second messenger cascades

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26
Q

These are the GABA receptors that are ligand gated

A

GABA-A

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27
Q

How many crosses of the membrane are there in a typical transmitter gated channel (not glutamate)?

A

4x for each subunit for a total of 20 crosses

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28
Q

How many GPCRs are known?

A

100

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29
Q

What does the letter m tell us about a receptor?

A

It lets us know the receptor is a GPCR

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30
Q

This amino acid NT acts through multiple ligand gated and GPCRs

A

Glutamate

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31
Q

What gets activated when a G protein is activated?

A

Effector systems (g alpha converts GTP to GDP to stop the action)

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32
Q

These receptors are made of 7 transmembrane region proteins

A

GPCRs

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33
Q

Along with AMPA, NMDA, and kainate inotropic receptors, this NT also has multiple GPCRs

A

Glutamate

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34
Q

SLIDE 45

A

SLIDE 45

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35
Q

What must bind for an ACh transmitter gated channel to open?

A

Two ACh

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36
Q

How is Ca entry important to a cell?

A

Important to many actions including learning and memory formation

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37
Q

How do NMDA channels depolarize to get to -35 mV to pop the Mg off and open?

A

Opening of AMPA channels nearby depolarizes them

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38
Q

This NT is removed form the synaptic cleft but EAAT (excitatory amino acid transporters, there are 5 of them) present in neurons and glia

A

Glutamate

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39
Q

Model channel is AChR from skeletal muscle

A

Transmitter gated channels

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40
Q

What are the two major types of G proteins?

A

Gs - stimulatory

Gi - inhibitory

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41
Q

This gas may also sometimes act as a NT like NO

A

Carbon monoxide (CO)

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42
Q

This gas NT is synthesized from arginine, released by some postsynaptic neurons, is a retrograde signal, and is membrane permeable

A

Nitric oxide (NO)

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43
Q

CB1 and CB2 for cannabinoids

A

GPCR

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44
Q

This AA NT acts through multiple ligand gated and multiple GPCRs

A

GABA

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45
Q

What NTs transmitter gated channels are an exception to the normal?

A

Glutamate

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46
Q

Muscarinic GPCRs (M1-M5)

A

ACh

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47
Q

Vitamin B6 is required as a cofactor for synthesis of this NT

A

GABA

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48
Q

These are composed of 5 subunits

A

Transmitter gated channels

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49
Q

These channels are involved in many systems and diseases

A

Amino acid gated channels

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50
Q

What accounts for ligand binding in transmitter gated channels?

A

Unique differences (Na, K, Ca, Cl, etc permeability)

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51
Q

These consist of alpha, beta, and gamma subunits

A

g proteins

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52
Q

These receptors are Cl channels similar to the nAChR

A

GABA-A and Glycine

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53
Q

What removes glycine from the synaptic cleft?

A

Plasma membrane glycine transporters

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54
Q

How is the G protein action stopped?

A

When it is activated the effector systems are activated and G alpha converts GTP to GDP to stop the action

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55
Q

These NTs bind to CB1 receptors that are GPCRs

A

Endocannabinoids

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56
Q

5HT1-5

A

GPCR

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57
Q

Activation of these glutamate receptors causes Na entry and depolarization and they coexist with NMDA receptors at the synapse

A

AMPA

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58
Q

There can be more than one kind of this NT in a single vesicle

A

Peptide NTs

59
Q

These NTs are processed more like proteins than classical small NTs

A

Peptide NTs

60
Q

These receptors mediate inhibitory action in the spinal cord and elsewhere

A

Glycine receptors

61
Q

This special NT opens cation channels (it is a nucleotide receptor)

62
Q

This AA NT is loaded into vesicles by vesicular inhibitory amino transporters (VIAAT) just like GABA

63
Q

This amino acid NT is involved in many circuits including learning, memory, and motor functions

64
Q

This gas NT is a retrograde signal and is membrane permeable

A

Nitric oxide (NO)

65
Q

What does each transmitter gated channel subunit have?

A

4 hydrophobic alpha-helical membrane spanning regions

66
Q

This is a marker for GABAergic neurons

A

Glutamic acid decarboxylase (GAD)

67
Q

These NTs are often co-released with small molecule transmitters

A

Peptide NTs

68
Q

What are heteromeric transmitter gated channels?

A

Channels with subunits of different types (a4b2, etc)

69
Q

This NT is not in vesicles and it is membrane permeable

A

Endocannabinoids

70
Q

This NT plays a role in development, neuroplasticity, and perhaps a role in AD

71
Q

These neurons are present mostly in local circuit interneurons but some can be on projection neurons (Purkinje cells)

72
Q

GDP is bound to this on the inside of the membrane

A

G alpha subunit (G protein)

73
Q

These two types of purine receptors are widespread

A

ATP and adenosine

74
Q

How are G proteins activated in GPCRs?

A

They are activated when the NT binds to the extracellular loop

75
Q

These channels include channels for glutamate, GABA, and glycine

A

Amino acid gated channels

76
Q

This special NTs function through retrograde signaling

A

Endocannabinoids

77
Q

These neurons are implicated in ALS

A

Glutamatergic neurons

78
Q

What do all different subtypes of transmitter gated channels have that make them important?

A

Different biophysical (opening quick or slow, etc) and pharmacological (NT concentration needed to bind, etc) properties

79
Q

These receptors are responsible for most inhibition in the CNS

A

GABA-A and Glycine

80
Q

alpha 1-2 and beta 1-3 for NE

81
Q

What does each transmitter gated channel subunit have?

A

4 transmembrane regions (except for glutamate)

82
Q

This is the major inhibitory NT

83
Q

G protein coupled system that allows the G protein to bind to ion channels, provides fastest signaling for GPCRs (30-100 msec), and is localized

A

Shortcut pathway

84
Q

It is important to know the 7 transmembrane proteins of these don’t form a channel

85
Q

These neurons are not present in peripheral tissues or nerves

86
Q

When do NMDA channels open by popping off the Mg?

87
Q

There are over 100 of these NTs (like endorphins, substance P, etc)

A

Peptide NTs

88
Q

These are composed of 4 types of subunits (alpha, beta, gamma, sigma)

A

Transmitter gated channels 5 subunits

89
Q

These neurons are present in many areas of the brain (third of synapses) and spinal cord

90
Q

These channels mediate fast synaptic transmission in the CNS

A

Amino acid gated channels

91
Q

Where do benzodiazepines, barbiturates, ethanol, and neurosteroids bind on the GABA-A receptor?

A

Allosteric sites (change function of channel but don’t open and close it)

92
Q

How does the G protein split up when activated?

A

g alpha + GTP and G beta + G gamma

93
Q

What types of sites have allosteric binding at them?

A

NCB sites (non competitive binding)

94
Q

Where do ligands bind on GPCRs?

A

Extracellular loop forms a binding site for them

95
Q

This AA NT acts through multiple ligand gated ion channels only

96
Q

These NTs act through GPCRs only

A

Peptide NTs

97
Q

What subunit is required for the binding site of an ACh transmitter gated channel?

98
Q

Can activated G proteins stimulate multiple pathways?

99
Q

9 of these subunits labeled 2-10

100
Q

How are amino acids used as NTs in neurons stored?

A

They are packaged into synaptic vesicles

101
Q

Where is L-glutamic acid-1-decarboxylase (GAD) mostly present

A

GABAergic neurons

102
Q

These glutamate channels are permeable to Ca and Ca entry is important to many actions in the cell including learning and memory formation

103
Q

How can activated G proteins stimulate multiple pathways?

A

The G alpha subunit can break down a molecule with an enzyme and the two parts of that molecule can stimulate different pathways

104
Q

Do different g proteins cause different effects?

105
Q

What does binding at an allosteric site cause?

A

Doesn’t open or close the channel but it influences the opening and closing of the channel (influences channel properties)

106
Q

The inotropic receptors for this NT include AMPA, NMDA, and kainate

107
Q

These receptors are ligand gated Cl channels similar in structure to GABA-A receptors and nAChRs

A

Glycine receptors

108
Q

This amino acid NT is not present in protein synthesis and thus not present in all cells

A

Gamma amino butyric acid (GABA)

109
Q

These transmitter gated receptors are similar to nAChRs but only have 4 subunits

A

Glutamate (AMPA, NMDA, and kainate)

110
Q

GABA-B Receptor

111
Q

Most excitatory neurons are this type and they are present at half of all synapses in the brain

A

Glutamatergic neurons

112
Q

What does changing one type of subunit in the transmitter gated channel cause?

A

It changes how the channel works

113
Q

Metabotropic GPCRs (mGluR1-8)

114
Q

These two are involved in many second messenger cascades

A

Kinases (add phosphates) and phosphatases (take off phosphates)

115
Q

What causes the transmitter gated channel to be closed and then to open?

A

Hydrophobic interactions of the subunits keep it closed and when the ligand (NT) binds, polarity is created and there is conformational changed that creates an opening

116
Q

These are the only transmitter gated channels that allow anions through, all the other allow cations through

A

GABA and Glycine

117
Q

The GABA receptor that is a GPCR

118
Q

What part of the g protein binds to the ion channel in the shortcut pathway?

A

The G beta + G gamma subunit

119
Q

How are different subtypes distributed throughout the brain?

A

They are seen in specific regions of the brain, different subtypes are distributed in different regions

120
Q

These glutamate receptors are permeable to Na and K but most aren’t to Ca

121
Q

Excitotoxicity by this NT can occur during a stroke

122
Q

How do endocannabinoids function uniquely compared to other NTs?

A

Ca enters the postsynaptic cell and activates an enzyme to create the endocannabinoid from the postsynaptic cell which then goes back to the presynaptic cell (retrograde) and binds to the CB1 receptor on the presynaptic cell

123
Q

What are the G proteins in GPCRs and how many are there?

A

20 kinds. Guanosine triphosphate (GTP) binding proteins

124
Q

How many EAATs are there and where are they found?

A

5 of them in neurons and glia

125
Q

How many transmembrane regions are in transmitter gated channels?

126
Q

This AA NT is present in half of the inhibitory synapses in the spinal cord

127
Q

This enzyme is not present in glutamatergic neurons or glia

A

Glutamic acid decarboxylase (GAD)

128
Q

Each subunit in a transmitter gated channel has a unique one of these

A

Unique sequence but are similar

129
Q

What do all different subtypes do?

A

They play different functional roles

130
Q

Can different transmitter gated channels (subtypes) be postsynaptic? Presynaptic? On neurons releasing other NTs?

A

Yes to all

131
Q

mu, sigma, and kappa for enkephalin

132
Q

These types of receptors have 2 GPCR families (A type and P type)

A

Purine NT receptors

133
Q

How can different GPCRs produce different effects?

A

Different GPCRs have different G proteins bound and the g proteins produce different effects (excite, inhibit, second messengers, etc)

134
Q

These are modulators of GABA receptors and can be used to treat epilepsy

A

Barbiturates

135
Q

These receptors have alpha binding subunits and beta nonbonding subunits

A

GABA-A and Glycine channels

136
Q

Where do NTs bind on transmitter gated channels?

A

Binding pockets located in the subunits towards the top of the channel

137
Q

What binds to a membrane bound enzyme to activate a second messenger cascade in GPCRs?

A

The G alpha subunit of the g protein

138
Q

These are the GABA receptors that are GPCRs

139
Q

What are homomeric transmitter gated channels?

A

Channels with subunits of the same type (a7)

140
Q

This NT is involved in learning and memory (long term potentiation)

141
Q

This is synthesized from glutamate by L-glutamic acid-1-decarboxylase (GAD)

142
Q

How are all ligand gated channels related?

A

They share common ancestors with each other on a phylogenetic tree

143
Q

This NT inhibits presynaptic Ca2+ channels

A

Endocannabinoids

144
Q

Most transmitter gated channels structures are similar to this

A

nAChR transmitter gated channel

Neuro 3000 (15 decks)

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