36. Drug Action on GABA and Receptors Flashcards
Describe GABA.
Gamma-Amino Butyric Acid, an amino acid
* GABA is a chief inhibitory neurotransmitter in the CNS
* principle role: reducing neuronal exicitability throughout the nervous system + regulate muscle tone
What is the main location of GABA in the CNS?
Amygdala
What is the function of GABA in the CNS?
Excitatory neurons in the amydgala fire to send excitatory signals to other areas of the brain.
* result: anxiety and fear
GABA can be released to inhibit excitatory signals
* result: calming effect
Where is GABA synthesized?
GABA is unable to cross the BBB –> must be synthesized from glutamate in the neurons in the brain.
Explain the human diseases associated with abnormal levels of GABA.
- epilepsy seizure
- anxiety disorder
- schizophrenia
Explain the biosynthesis of GABA: Step 1.
In the mitochondrion, glutamine (Gln) is converted to glutamate (Glu) by glutaminase.
Explain the biosynthesis of GABA: Step 2.
GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD).
Describe the process of GABA storage: Step 3.
GABA is uptake into vesicles by vesicular GABA transporter (vGAT).
Describe the release process of GABA: Step 4.
Under stimulation by Ca2+, vesicles infuse with presynaptic membrane and release GABA to synaptic cleft during exocytosis.
Describe the process of GABA reuptake: Step 5/6.
GABA is reuptake by GABA transporter (GAT) back to vesicles in presynaptic neuron for reuse.
* GABA is uptake into glial cells via GAT
Describe the degradation process of GABA: Step 7/8.
- In the glial cells, GABA is converted to glutamate by GABA transminase (GABA-T) in mitochondrion.
- Glutamate is converted to glutamine by glutamine synthase.
Describe the process of glutamine reuptake: Step 9.
Glutamine is transported back to presynaptic neuron by glutamine transporter.
* glutamine can be reused for GABA synthesis
Describe the difference between GABA and glutamate.
GABA - calming neurotransmitter
Glutamate - excitatory neurotransmitter
Explain the effects of too much glutamate.
Anxiety, perserervating, restlessness, migraines, tics, motor stereotypies (flapping/stimming)
Explain the effects of too much glutamate.
Anxiety, perserervating, restlessness, migraines, tics, motor stereotypies (flapping/stimming)
Explain the process of GABA signaling in the postsynaptic neuron.
GABAs move across the synaptic cleft and bind to GABA receptors in postsynaptic neuron for signaling
GABA receptors:
* GABAaR: ionotropic receptors
* GABAbR: metabotropic receptors
Explain what happens when GABAaR is activated by GABA.
Results in translocation of Cl- ions into postsynaptic neuron, making the cell hyperpolarize and inhibiting action potentials.
* Cl- ions make the neuron harder to be stimulated by other neurotransmitters, thus slowing down its activity and making the person feel more relaxed.
e. amygdala
C. GABA transporter on presynaptic membrane.
b. seven-pass transmembrane domains
d. efflux of Cl- ions from postsynaptic neuron
* GABAaR receptors trigger influx of Cl- ions into postsynaptic neuron,
a. activation of Ca2+ channels
* inhibits Ca2+ uptake
* activate K+ ion channels
d. bicuculline
* GABAaR antagonist
