Glutamate & GABA Flashcards
What type of neurotransmitter is glutamate?
Excitatory
What type of neurotransmitter is GABA?
Inhibitory
Do you take up neurotransmitters in your diet?
No, you take up precursors then the brain makes the neurotransmitter wherever it is needed
What type of signalling occurs from the presynaptic terminal- synaptic cleft- Post synaptic cell?
- Electrical impulse occurs across the presynaptic terminal
- Chemical signalling occurs across the synaptic cleft
- Electrical impulse occurs across the post synpatic cell
Describe the 2S,3R,2D (SSRRRDD) system
S: Synthesis S:Storage R:Release R:Receptors R:Reuptake D:Degradation D:Drugs& disease
Outline the characteristics of glutamate
- Amino acid
- Widely distributed in the CNS 70% of all synapses
- Very little in the PNS
- The most important excitatory NT in the CNS
Outline the synthesis of glutamate
In the neurone Glutamine is converted to glutamate via the enzyme glutaminase
How and where is glutamate converted into glutamine
Glutamate is converted into glutamine via the enzyme glutamine synthase in the glia
How are glutamate and GABA connected
Glutamate is converted into alpha-ocoglutarate using the enzyme transaminase
-Alpha-oxoglutarate is converted into glutamate using GABA transaminase
Outline the storage of Glutamate and explain how this is made possible
- Packaged into vesicles
- This is made possible as the vesicle contains a vesicle glutamate transporter (3 different types)
- The glutamate is transported against its concentration gradient into the vesicles as there’s a transporter that removes 2 h+ ions from the cell in replace of a glutamate molecule entering the vesicle
- The acidic env of the cell is achieved by a proton pump which uses the conversion of ATP to ADP to move h+ ions against their conc gradients
Describe the release of glutamate
Calcium dependent vesicular release at the axon end terminal bouton
-A depolarisation along the pre-synpatic neurone opens voltage dependant calcium channels. Calcium flows into the cell across its huge conc gradient
Outline the different receptors involved in glutamate transmission
- ) Ionotropic receptors iGluR (ion channels activated by glutamate)
- NMDA cation channel na+ k+ ca2+
- AMPA cation channel Na+ K+ (Some ca2+)
- Kainate cation channel Na K+ - ) Metabotropic receptors mGluR ( G-protein coupled receptors, class C)
- Interfere with the metabolism of the cell
- Group I- mGluR1 & mGluR5 couple to Gq & G11 G proteins
- Group II- mGluR2 & mGluR3 couple to Go& Gi G-proteins
- Group III- mGluR4 & mGluR6-8 couple to Go& Gi G proteins
What are the differences in characteristics between G protein coupled receptors and ionotropic recepotrs?
G protein coupled receptors are slower because the receptor has to bind to glutamate and interact with a 2nd messenger system before having an effect
Outline the structure of the iGLUR receptor
- 3 transmembrane units
- 4 subunits; heterotetramer
- Binding site for glutamate on N terminals
Outline the structure of the mGluR receptor
7 transmembrane proteins
-Binding site for glutamate on N terminals
Outline the reuptake of glutamate
- In the astrocyte glutamate is converted to glutamine using glutamine synthase
- Glutamine transporters present on the astrocyte and neurone allow the glutamine to be transported into the neurone
- Glutaminase is used to convert glutamine back to glutamate
- Excitatory amino acid transporters present on the neurone and glial cell also allow glutamate to be taken up
Outline the degradation of glutamate
- Excitatory amino acid transporters present on the neurone and glial cell allow glutamate to be taken up. This allows for removal from the synaptic cleft
- Converted to glutamine by glutamine synthase in astrocytes
- The glutamine is transferred to the neurone where it is converted back to glutamate by glutaminase to be reused
Describe which drugs affect the transmission of glutamate
- ) Ketamine( NMDA channel blocker)
- ) Memantine ( NMDA competitive antagonist)
- Used in AD to reduce neurodegenration of nerve cells in the brain - ) Perampanel( noncompetitibe AMPA anatagonist)
- useful anti-epileptic agent
Describe the disease associated with Glutamate
Recreational drugs:
-phencyclidine (PCP) ‘angel dust@
disease: epilepsy-critical to all CNS function
- AD
- Drug abuse
- Anaesthesia
Outline the characteristics of GABA(Gamma Aminobutyric acid )
- AA
- Widely distributed in the CNS (30% of synpases)
- Very little in the PNS
- The most important inhibitory NT in the CNS
Describe the synthesis of GABA
-Glutamate is the precursor and it is converted to GABA using the enzyme GAD( Glutamic acid decarboxylase)
Describe the storage of GABA
- Similar idea to glutamate
- vesicular GABA transporter (vGABAT) transports a GABA molecule into the vesicle in exchange for two protons
- proton pump creates acidic environment using energy from conversion of ATP to ADP
Describe the release of GABA
calcium dependent vesicular release axon end terminal bouton
Outline the receptors involved in transmission of GABA
- ) Ionotropic receptors ( ion channels activated by GABA)
- GABA(A) receptor: anion channel Cl- - ) Metabotropic ( G-protein coupled receptors activated by GABA, class C)
- GABA(B) receptors couple to Gi & Go G-proteins
Describe the structure of receptors for GABA
- ) GABA(A):ionotropic receptor; 4 transmembrane regions; 5 subunits; when GABA binds it opens the cl- pore
- ) GABA(B): 7 transmembrane regions
What effect do benzos have on GABA receptors?
- Enhance the effect of GABA
- -specific site for benzos to act on the GABAa receptor, they enhance its effect
- Result in sedative, hypnotic, anxiolytic, anticonvulsant & muscle relaxant properties
- eg diazepam & midazolam
Describe the reuptake of GABA
- ) GAT1 = neuronal GABA transporter (requires na+)
2. ) GAT3= Glial GABA transporter
Outline the degradation of GABA
- Mostly occurs in glia
- Using the enzyme GABA transaminase GABA is converter to succinic semialdehyde
- Using the enzyme GABA transaminase, alpha-oxoglutarate is converted to glutamate
Outline the Drugs that may act on different stages of GABA transmission
- ) acting on the receptors:
- GABA(A) muscimol( agonist); bicuculline (competitive antagonist); picrotoxin (channel blocker); benzos; ethanol and some general anaesthetics(propofol are all positive allosteric modulators (PAMs)
- GABA(B) baclofen(agonist); saclofen (competitive antagonist)
- Reuptake tiagabine (blocks GAT)
- degradation vigabatrine ( blocks GABA-transaminase)
Outline the recreation drugs associated with GABA
- Barbiturates “Downers”
- Nitrous oxide “laughing gas”
Outline the diseases that may be associated with problems with GABA
- epilepsy
- anxiety
- insomnia
- muscle tone
