Neurotransmitter Systems Part 2 Flashcards
What do benzodiazepines (valium) and barbiturates (phenobarbtiol) do?
Act on GABA-A and Glycine channels
benzo = inc freq of opening
barbs = inc channel open time
This NT is removed from the synapse by high affinity transporters (GATs) into neurons and glia
GABA
This AA NT is broken down in mitochondria
GABA
SLIDE 60
SLIDE 60
D1-5
GPCR
This amino acid NT is packaged into synaptic vesicles by a vesicular inhibitory amino acid transporter (VIAAT)
GABA
How are subtypes for transmitter gated channels important in drug development?
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
How can a GPCR amplify a signal?
The ligand binding can impact multiple G proteins which impact multiple pathways which impact multiple cascades and so on (SLIDE 61)
Where do G proteins bind on GPCRs?
Some of the intracellular loop
SLIDE 62
SLIDE 62
This purine NT is excitatory in sensory and autonomic ganglia in motor neurons
ATP
Signaling deficits of this NT are associated with Huntington’s, Parkinson’s, schizo, and senile dementia
GABA
This NT is synthesized from serine by serine hydroxymetyltransfrase
Glycine
Strychnine is an antagonist of this receptor
Glycine receptors
These types of receptors have one ligand gated family (P2X1-P2X7) and two transmembrane domains
Purine NT receptors
3 of these subunits labeled 2-4
beta
The channel of these glutamate receptors is blocked by Mg at -65 mV (inward current is voltage dependent)
NMDA
What do different subunits create in transmitter gated channels and how do those then have an effect on the channel?
Subunits create different subtypes which have different affinities for NTs (one subtype may allow binding at a lower concentration, higher concentration, etc)
Two types of this NT include anandamide and 2-arachidonylglycerol (2-AG)
Endocannabinoids
This is an endogenous protein that is similar to cobra venom
Lynx1 protein
These transmitter gated channels only have 4 subunits
Glutamate
These receptors are modulated by benzodiazepines (valium) to inc frequency of opening and barbiturates (phenobarbital) to inc channel open time
GABA-A and Glycine channels
These two NTs are used in the synthesis of proteins and thus present in all cells
Glutamate and glycine
What can a dietary deficiency of vitamin B6 lead to?
Lower levels of GABA synthesis which can lead to seizures
A G protein coupled system that involves multiple steps and the activation of enzymes
Second messenger cascades
These are the GABA receptors that are ligand gated
GABA-A
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
How many GPCRs are known?
100
What does the letter m tell us about a receptor?
It lets us know the receptor is a GPCR
This amino acid NT acts through multiple ligand gated and GPCRs
Glutamate
What gets activated when a G protein is activated?
Effector systems (g alpha converts GTP to GDP to stop the action)
These receptors are made of 7 transmembrane region proteins
GPCRs
Along with AMPA, NMDA, and kainate inotropic receptors, this NT also has multiple GPCRs
Glutamate
SLIDE 45
SLIDE 45
What must bind for an ACh transmitter gated channel to open?
Two ACh
How is Ca entry important to a cell?
Important to many actions including learning and memory formation
How do NMDA channels depolarize to get to -35 mV to pop the Mg off and open?
Opening of AMPA channels nearby depolarizes them
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
Model channel is AChR from skeletal muscle
Transmitter gated channels
What are the two major types of G proteins?
Gs - stimulatory
Gi - inhibitory
This gas may also sometimes act as a NT like NO
Carbon monoxide (CO)
This gas NT is synthesized from arginine, released by some postsynaptic neurons, is a retrograde signal, and is membrane permeable
Nitric oxide (NO)
CB1 and CB2 for cannabinoids
GPCR
This AA NT acts through multiple ligand gated and multiple GPCRs
GABA
What NTs transmitter gated channels are an exception to the normal?
Glutamate
Muscarinic GPCRs (M1-M5)
ACh
Vitamin B6 is required as a cofactor for synthesis of this NT
GABA
These are composed of 5 subunits
Transmitter gated channels
These channels are involved in many systems and diseases
Amino acid gated channels
What accounts for ligand binding in transmitter gated channels?
Unique differences (Na, K, Ca, Cl, etc permeability)
These consist of alpha, beta, and gamma subunits
g proteins
These receptors are Cl channels similar to the nAChR
GABA-A and Glycine
What removes glycine from the synaptic cleft?
Plasma membrane glycine transporters
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
These NTs bind to CB1 receptors that are GPCRs
Endocannabinoids
5HT1-5
GPCR
Activation of these glutamate receptors causes Na entry and depolarization and they coexist with NMDA receptors at the synapse
AMPA