Lecture 13 - GABA (GABAa) Flashcards
What is GABA?
-[predominant] inhibitory amino acid neurotransmitter (the one we know most about)
-adj: GABAergic
-[there is also Glycine)
When did GABA get identified as a NT?
-in 1950 agreed that GABA was a NT
-both a step in metabolic processes and NT [took a long time to show this]
-main inhibitory input across the nervous systems
What are the 2 types of GABA neurons?
- projection neuron: cell body is in one area of the brain [nucleus] and its axon and terminals project to another nucleus or area of the brain
- interneurons: neurons that stay within the same brain area/nucleus within the central nervous system
How does GABA synthesis work?
-GABA is synthesized from Glu by an enzyme called GAD [Glutamic Acid Decarboxylase]
-then it is taken up in the vesicles by GAT [Vesicular GABA transporter]
How does GABA release and signal termination work?
2 modes of signal termination:
-enzymes within the synaptic cleft called GABA-T [GABA Transaminase] metabolize GABA back into Glu;
-it can be reuptaken by another form of the GAT into glia cells (they take GABA and store it) or pre-synaptic cell (like Glu)
What are the different kinds of GABA receptors?
-LGICs –> GABAa
-GPCRs –> GABAb (both pre and post-synaptic)
What are the characteristics of GABAa receptor?
-GABAa receptor is permeable to Cl-, meaning that once its activated and the channel opens, its gonna hyperpolarize the membrane (to stop neuron from firing)
-GABA [active] binding site
-BDZ [benxodiazepine] site (anxiolytics; e.g., valium)
-barbiturate site (sleeping pills/sedatives)
-steroid site (anesthetics)
-picarotoxin site [channel blocking site] (convulsants & depressants)
What happens when GABA binds to the active site on GABAa receptor?
-conformational change opens the central channel
-Cl- ions flow into the membrane, preventing the membrane from firing and reaching threshold
What happens when barbiturates bind to the barbiturate site?
-when barbiturates bind to the site, they cause a confirmational change in GABAa receptor such that it opens the channel (even without GABA binding to its active site)
-barbiturate does not need the help of GABA to increase the inhibition on the membrane can open the GABAa channel by itself
What happens when GABA is bound to active site at same time as bdz is bound to its site?
-if GABA is bound at the same time as bdz, the bdz will open the channel longer or wider
-enhances the effect of GABA [inhibition production]
-GABA needs to be bound too for bdz to have any effect
What are barbiturates and benzodiazepines used for? What are their effects?
-barbiturates put you to sleep/sedate you
-benzodiazepines can have an effect on sleep, but they are used for anxiety (to calm us down)
What are the characteristics of alcohol?
-alcohol is considered a sedative but it is very dose-dependent
-because alcohol in smaller doses is not a sedative, it is more activating/exciting (ex: help socialize)
-as dose increases, because more of a sedative; slurred speech, pass out
-also alcohol is not a molecule that binds to a receptors (why we don’t know much)
What are the effects of acute alcohol on GABA?
-acute alcohol consumption potentiates GABA currents
-it somehow enhances the effects of the GABA NT’s neurotransmission (alcohol has an inhibitory effect on the central nervous system)
What happens there is chronic alcohol consumption?
-chronic alcohol can decrease GABAa receptors [downregulation] and increase NMDA receptors [upregulation]
-because the brain is compensating for the fact that there is too much inhibition in the CNS
What is the consequence of too many Cl- ions flowing in our nervous system?
-coma
-OD
-death
