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
2
Q
This NT is removed from the synapse by high affinity transporters (GATs) into neurons and glia
A
GABA
3
Q
This AA NT is broken down in mitochondria
A
GABA
4
Q
SLIDE 60
A
SLIDE 60
5
Q
D1-5
A
GPCR
6
Q
This amino acid NT is packaged into synaptic vesicles by a vesicular inhibitory amino acid transporter (VIAAT)
A
GABA
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
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)
9
Q
Where do G proteins bind on GPCRs?
A
Some of the intracellular loop
10
Q
SLIDE 62
A
SLIDE 62
11
Q
This purine NT is excitatory in sensory and autonomic ganglia in motor neurons
A
ATP
12
Q
Signaling deficits of this NT are associated with Huntington’s, Parkinson’s, schizo, and senile dementia
A
GABA
13
Q
This NT is synthesized from serine by serine hydroxymetyltransfrase
A
Glycine
14
Q
Strychnine is an antagonist of this receptor
A
Glycine receptors
15
Q
These types of receptors have one ligand gated family (P2X1-P2X7) and two transmembrane domains
A
Purine NT receptors
16
Q
3 of these subunits labeled 2-4
A
beta
17
Q
The channel of these glutamate receptors is blocked by Mg at -65 mV (inward current is voltage dependent)
A
NMDA
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)
19
Q
Two types of this NT include anandamide and 2-arachidonylglycerol (2-AG)
A
Endocannabinoids
20
Q
This is an endogenous protein that is similar to cobra venom
A
Lynx1 protein
21
Q
These transmitter gated channels only have 4 subunits
A
Glutamate
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
23
Q
These two NTs are used in the synthesis of proteins and thus present in all cells
A
Glutamate and glycine
24
Q
What can a dietary deficiency of vitamin B6 lead to?
A
Lower levels of GABA synthesis which can lead to seizures
25
A G protein coupled system that involves multiple steps and the activation of enzymes
Second messenger cascades
26
These are the GABA receptors that are ligand gated
GABA-A
27
How many crosses of the membrane are there in a typical transmitter gated channel (not glutamate)?
4x for each subunit for a total of 20 crosses
28
How many GPCRs are known?
100
29
What does the letter m tell us about a receptor?
It lets us know the receptor is a GPCR
30
This amino acid NT acts through multiple ligand gated and GPCRs
Glutamate
31
What gets activated when a G protein is activated?
Effector systems (g alpha converts GTP to GDP to stop the action)
32
These receptors are made of 7 transmembrane region proteins
GPCRs
33
Along with AMPA, NMDA, and kainate inotropic receptors, this NT also has multiple GPCRs
Glutamate
34
SLIDE 45
SLIDE 45
35
What must bind for an ACh transmitter gated channel to open?
Two ACh
36
How is Ca entry important to a cell?
Important to many actions including learning and memory formation
37
How do NMDA channels depolarize to get to -35 mV to pop the Mg off and open?
Opening of AMPA channels nearby depolarizes them
38
This NT is removed form the synaptic cleft but EAAT (excitatory amino acid transporters, there are 5 of them) present in neurons and glia
Glutamate
39
Model channel is AChR from skeletal muscle
Transmitter gated channels
40
What are the two major types of G proteins?
Gs - stimulatory
| Gi - inhibitory
41
This gas may also sometimes act as a NT like NO
Carbon monoxide (CO)
42
This gas NT is synthesized from arginine, released by some postsynaptic neurons, is a retrograde signal, and is membrane permeable
Nitric oxide (NO)
43
CB1 and CB2 for cannabinoids
GPCR
44
This AA NT acts through multiple ligand gated and multiple GPCRs
GABA
45
What NTs transmitter gated channels are an exception to the normal?
Glutamate
46
Muscarinic GPCRs (M1-M5)
ACh
47
Vitamin B6 is required as a cofactor for synthesis of this NT
GABA
48
These are composed of 5 subunits
Transmitter gated channels
49
These channels are involved in many systems and diseases
Amino acid gated channels
50
What accounts for ligand binding in transmitter gated channels?
Unique differences (Na, K, Ca, Cl, etc permeability)
51
These consist of alpha, beta, and gamma subunits
g proteins
52
These receptors are Cl channels similar to the nAChR
GABA-A and Glycine
53
What removes glycine from the synaptic cleft?
Plasma membrane glycine transporters
54
How is the G protein action stopped?
When it is activated the effector systems are activated and G alpha converts GTP to GDP to stop the action
55
These NTs bind to CB1 receptors that are GPCRs
Endocannabinoids
56
5HT1-5
GPCR
57
Activation of these glutamate receptors causes Na entry and depolarization and they coexist with NMDA receptors at the synapse
AMPA
58
There can be more than one kind of this NT in a single vesicle
Peptide NTs
59
These NTs are processed more like proteins than classical small NTs
Peptide NTs
60
These receptors mediate inhibitory action in the spinal cord and elsewhere
Glycine receptors
61
This special NT opens cation channels (it is a nucleotide receptor)
ATP
62
This AA NT is loaded into vesicles by vesicular inhibitory amino transporters (VIAAT) just like GABA
Glycine
63
This amino acid NT is involved in many circuits including learning, memory, and motor functions
Glutamate
64
This gas NT is a retrograde signal and is membrane permeable
Nitric oxide (NO)
65
What does each transmitter gated channel subunit have?
4 hydrophobic alpha-helical membrane spanning regions
66
This is a marker for GABAergic neurons
Glutamic acid decarboxylase (GAD)
67
These NTs are often co-released with small molecule transmitters
Peptide NTs
68
What are heteromeric transmitter gated channels?
Channels with subunits of different types (a4b2, etc)
69
This NT is not in vesicles and it is membrane permeable
Endocannabinoids
70
This NT plays a role in development, neuroplasticity, and perhaps a role in AD
Glutamate
71
These neurons are present mostly in local circuit interneurons but some can be on projection neurons (Purkinje cells)
GABAergic
72
GDP is bound to this on the inside of the membrane
G alpha subunit (G protein)
73
These two types of purine receptors are widespread
ATP and adenosine
74
How are G proteins activated in GPCRs?
They are activated when the NT binds to the extracellular loop
75
These channels include channels for glutamate, GABA, and glycine
Amino acid gated channels
76
This special NTs function through retrograde signaling
Endocannabinoids
77
These neurons are implicated in ALS
Glutamatergic neurons
78
What do all different subtypes of transmitter gated channels have that make them important?
Different biophysical (opening quick or slow, etc) and pharmacological (NT concentration needed to bind, etc) properties
79
These receptors are responsible for most inhibition in the CNS
GABA-A and Glycine
80
alpha 1-2 and beta 1-3 for NE
GPCR
81
What does each transmitter gated channel subunit have?
4 transmembrane regions (except for glutamate)
82
This is the major inhibitory NT
GABA
83
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
Shortcut pathway
84
It is important to know the 7 transmembrane proteins of these don't form a channel
GPCRs
85
These neurons are not present in peripheral tissues or nerves
GABAergic
86
When do NMDA channels open by popping off the Mg?
-35 mV
87
There are over 100 of these NTs (like endorphins, substance P, etc)
Peptide NTs
88
These are composed of 4 types of subunits (alpha, beta, gamma, sigma)
Transmitter gated channels 5 subunits
89
These neurons are present in many areas of the brain (third of synapses) and spinal cord
GABAergic
90
These channels mediate fast synaptic transmission in the CNS
Amino acid gated channels
91
Where do benzodiazepines, barbiturates, ethanol, and neurosteroids bind on the GABA-A receptor?
Allosteric sites (change function of channel but don't open and close it)
92
How does the G protein split up when activated?
g alpha + GTP and G beta + G gamma
93
What types of sites have allosteric binding at them?
NCB sites (non competitive binding)
94
Where do ligands bind on GPCRs?
Extracellular loop forms a binding site for them
95
This AA NT acts through multiple ligand gated ion channels only
Glycine
96
These NTs act through GPCRs only
Peptide NTs
97
What subunit is required for the binding site of an ACh transmitter gated channel?
Alpha
98
Can activated G proteins stimulate multiple pathways?
Yes
99
9 of these subunits labeled 2-10
alpha
100
How are amino acids used as NTs in neurons stored?
They are packaged into synaptic vesicles
101
Where is L-glutamic acid-1-decarboxylase (GAD) mostly present
GABAergic neurons
102
These glutamate channels are permeable to Ca and Ca entry is important to many actions in the cell including learning and memory formation
NMDA
103
How can activated G proteins stimulate multiple pathways?
The G alpha subunit can break down a molecule with an enzyme and the two parts of that molecule can stimulate different pathways
104
Do different g proteins cause different effects?
yes
105
What does binding at an allosteric site cause?
Doesn't open or close the channel but it influences the opening and closing of the channel (influences channel properties)
106
The inotropic receptors for this NT include AMPA, NMDA, and kainate
Glutamate
107
These receptors are ligand gated Cl channels similar in structure to GABA-A receptors and nAChRs
Glycine receptors
108
This amino acid NT is not present in protein synthesis and thus not present in all cells
Gamma amino butyric acid (GABA)
109
These transmitter gated receptors are similar to nAChRs but only have 4 subunits
Glutamate (AMPA, NMDA, and kainate)
110
GABA-B Receptor
GPCR
111
Most excitatory neurons are this type and they are present at half of all synapses in the brain
Glutamatergic neurons
112
What does changing one type of subunit in the transmitter gated channel cause?
It changes how the channel works
113
Metabotropic GPCRs (mGluR1-8)
Glutamate
114
These two are involved in many second messenger cascades
Kinases (add phosphates) and phosphatases (take off phosphates)
115
What causes the transmitter gated channel to be closed and then to open?
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
These are the only transmitter gated channels that allow anions through, all the other allow cations through
GABA and Glycine
117
The GABA receptor that is a GPCR
GABA-B
118
What part of the g protein binds to the ion channel in the shortcut pathway?
The G beta + G gamma subunit
119
How are different subtypes distributed throughout the brain?
They are seen in specific regions of the brain, different subtypes are distributed in different regions
120
These glutamate receptors are permeable to Na and K but most aren't to Ca
AMPA
121
Excitotoxicity by this NT can occur during a stroke
Glutamate
122
How do endocannabinoids function uniquely compared to other NTs?
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
What are the G proteins in GPCRs and how many are there?
20 kinds. Guanosine triphosphate (GTP) binding proteins
124
How many EAATs are there and where are they found?
5 of them in neurons and glia
125
How many transmembrane regions are in transmitter gated channels?
4
126
This AA NT is present in half of the inhibitory synapses in the spinal cord
Glycine
127
This enzyme is not present in glutamatergic neurons or glia
Glutamic acid decarboxylase (GAD)
128
Each subunit in a transmitter gated channel has a unique one of these
Unique sequence but are similar
129
What do all different subtypes do?
They play different functional roles
130
Can different transmitter gated channels (subtypes) be postsynaptic? Presynaptic? On neurons releasing other NTs?
Yes to all
131
mu, sigma, and kappa for enkephalin
GPCR
132
These types of receptors have 2 GPCR families (A type and P type)
Purine NT receptors
133
How can different GPCRs produce different effects?
Different GPCRs have different G proteins bound and the g proteins produce different effects (excite, inhibit, second messengers, etc)
134
These are modulators of GABA receptors and can be used to treat epilepsy
Barbiturates
135
These receptors have alpha binding subunits and beta nonbonding subunits
GABA-A and Glycine channels
136
Where do NTs bind on transmitter gated channels?
Binding pockets located in the subunits towards the top of the channel
137
What binds to a membrane bound enzyme to activate a second messenger cascade in GPCRs?
The G alpha subunit of the g protein
138
These are the GABA receptors that are GPCRs
GABA-B
139
What are homomeric transmitter gated channels?
Channels with subunits of the same type (a7)
140
This NT is involved in learning and memory (long term potentiation)
Glutamate
141
This is synthesized from glutamate by L-glutamic acid-1-decarboxylase (GAD)
GABA
142
How are all ligand gated channels related?
They share common ancestors with each other on a phylogenetic tree
143
This NT inhibits presynaptic Ca2+ channels
Endocannabinoids
144
Most transmitter gated channels structures are similar to this
nAChR transmitter gated channel
