GABA & Glycine Flashcards
What is the criteria for being a neurotransmitter?
→ The molecule must be synthesized and stored in a presynaptic neuron
→ The molecule must be released by the presynaptic axon terminal upon stimulation
→ the molecule must produce a response in the post synaptic cell
What are the two main methods that inhibitory neurotransmitters use?
→ Influx of negative ions via chloride channels
→ Efflux of positive ions via potassium channels
Describe the conversion from Glutamate to GABA
→ Carboxylic acid group is removed from glutamate to make GABA
→ vitamin B6 (pyridoxal phosphate) acts as a cofactor
How is GABA transported into vesicles?
→ VIAAT
→ vesicular inhibitory amino acid transporters
What is the difference in shape between glutamate, GABA and glycine vesicles?
→ Glutamate vesicles are round
→ GABA or glycine vesicles are more oval in shape
Where are GABA A receptors found?
→ Postsynaptically
→ They can sometimes be found presynaptically on glia
What are the two ways that GABA can be broken down?
→ GABA transaminase
→ can diffuse away from the synapse
Between what two subunits does GABA bind?
→ Alpha and beta receptors
How many molecules of GABA are needed for the GABA A channels to open?
→ 2 molecules
Where is the benzodiazepine binding site found?
→ At the alpha and gamma interface of the GABA A receptor
What are channel modulators?
→ They increase the conductance of chloride through the GABA A channels such as alcohol
What is an example of a GABA A channel blocker?
→ Picrotoxin
What type of G protein is a GABA B receptor?
→ Gi protein channel
What are two major effects of the GABA B receptors?
→it opens K+ channels so it hyperpolarizes
→blocks calcium channels
What is another effect of the GABA B receptor?
→ It blocks Ca2+ channels
What are the 4 types of GABA A receptor enhancers?
→ Barbiturates
→ Benzodiazepines- positive allosteric modulations
→ Progesterone
→ Ganaloxone
What is an example of a GABA transaminase inhibitor?
→ Vigabatrine
How do the majority of epileptics work?
→ Increasing inhibition
→ Enhance the currents through GABA A
What is the transporter that takes GABA to the presynaptic terminal?
→ GAT
Neurons = GAT-1
Glial cells = GAT-3
Describe the steps for glycine synthesis
3-phosphoglycerate (glycolysis) ↓ serine (serine hydroxy methyl transferase) ↓ glycine
What are the subtypes of glycine receptors?
→ alpha 1 - 4
→ one beta subtype
How is glycine activity terminated?
→ Reuptake by glycine transporter GlyT
Glial cells = GlyT-1
Neurons = GlyT-2
What breaks down glycine?
→ serine hydroxymethyl-transferase
→ or it diffuses away from the synapse
Why is glycine difficult to target?
→ It is present on inhibitory receptors
→ Glycine is also needed for NMDA receptors which are excitatory
What gets activated if you use an agonist that has a similar shape to glycine?
→ Inhibitory and excitatory pathways are activated
What are the 4 glutamate receptors?
→ AMPA
→ NMDA
→ Kainate
→ MGlu R1-8s
In what 2 ways can glutamate be terminated?
→ Diffusion
→ EAATs
What are the 2 GABA receptors?
→ GABA A
→ GABA B
In what 3 ways can GABA be terminated?
→ Diffusion
→ GAT
→ Enzyme
What is the glycine receptor?
→ Glycine R
In what 3 ways can glycine be terminated?
→ Diffusion, GlyT, enzyme
What is the serotonin receptor?
→ 5-HT 1-7
What are the 3 ways serotonin can be terminated?
→ Diffusion
→ SERT
→ enzyme
What are the 2 receptors for ACh?
→ nAChR
→ mAChR
What kind of a receptor is GABA A?
→ ligand gated Cl-
What are the subunits of a GABA A receptor?
→ Six alpha subtypes (a1-6)
→ three beta subtypes (b1-3)
→ three gamma subtypes ( y1-3)
→ also delta, epsilon, pi and theta subunits
What is the typical configuration of a GABA A receptor?
→ pentameric structure
→ 2 alpha, 2 beta and 1 gamma
What are the components of the GABA B receptor?
→ GABAB 1 and GABA B2
What are the two types of GAT?
→ GAT1 is in neurons
→ GAT 3 is in glial cells
How is GABA degraded?
→ GABA → succinic semialdehyde
catalysed by gaba transaminase
→ succinic semialdehyde → succinic acid
catalysed by succinic semialdehyde dehydrogenase (SSADH)
What are the 5 types of drugs used to treat epilepsy?
→ GABA A receptor enhancers
→ GAT blockers
→ GABA transaminase inhibitor
→ GAD modulator
→ Prodrug
How is glycine transported into vesicles?
→ VIAAT
What is the most common configuration of the glycine receptor
→ 3a1 or 2 beta
OR
→ 4 alpha 1 and 1 beta
What are the two different types of Glyt and where are they found?
→ Glyt1 - glial cells
→ Glyt2 - neurons
Where are glycine receptors found?
→ Pre and post synaptically
What is hyperekplexia?
→ Disorder characterised by increased mucscle tone and a exaggerated startle response
How does hyperekplexia work?
→ no glycine protein at the postsynaptic membrane
→Can lead to neuronal hyperexcitability
What are purkinje cells?
a class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex
What does purkinje cells generate?
→error connection signal that can modify movements
→basis for real-time control of precise and synchronous movement
