House of Mind

"Biology gives you a brain. Life turns it into a mind" - Jeffrey Eugenides

  • 28th June
    2011
  • 28
GABA: The main inhibitory neurotransmitter in the central nervous system. 
GABA is considered part of the small neurotransmitter molecules (like acetylcholine and glutamate) and is synthesized directly in the axon terminal, near the release site.
GABA, along with its signaling components, receptors, enzymes, transporters, and such are present early in development. 
GABA is a multifunctional molecules with different situational roles throughout development. Functions include: influencing neural migration, acting as a neurotrophic factor and facilitating neurite extension/maturation. 
Glutamate is the precursor of GABA. Glutamate is converted into GABA by a decarboxylation reaction catalyzed by glutamic acid decarboxylase (GAD), a rate limiting enzyme in GABA synthesis that requires the cofactor pyridoxal phosphate (PLP).
Like glutamate, GABAergic neurotransmission relies on different kinds of receptors (i.e. ionotropic vs. metabotropic) that are characterized by pharmacological differences.
There are 3 GABA receptors: GABA-A, GABA-B, GABA-C.
GABA-A and GABA-C receptors are ionotropic and mediate fast (inhibitory) GABA responses by triggering calcium channel openings. In other words, they are ligand-gated calcium channels. Bicuculline is a GABA-A receptor antagonist. 
GABA-A receptors are classified according to their corresponding amino acid sequence. Additionally, many receptor subunits have been found and each has a unique distribution in the brain. The diversity of GABA-A receptor subtypes are thought to highlight their great importance in the regulation of brain excitability. GABA-A receptors also include binding sites for other clinically relevant drugs (i.e. benzodiazepines).
GABA-B receptors are metabotropic receptors that are a part of the g-protein coupled receptor (GPCRs) family and mediate slower GABA responses by activating G-proteins to influence second messenger systems. These mostly regulate calcium and potassium channel openings to mediate the long-term inhibitory actions of GABA. Moreover, GABA-B receptors are present pre and post-synaptically. Baclofen is a GABA-B receptor antagonist. 
GABA-B receptors play an important role in long term inhibition of synaptic transmission. GABA-B autoreceptors control the release of GABA while GABA-B heteroreceptors control the release of glutamate, noradrenaline, dopamine, substance P and others. Finally, GABA-B receptor distribution is different than GABA-A receptor distribution in the brain. 
GABA-C receptors have a similar structure (pentameric chloride sensitive channels) and composition (different subunits) similar to GABA-A receptors, but vary in their kinetic and pharmacological properties. However, they have greater sensitivity to GABA compared to GABA-A receptors. GABA-C receptors are insensitive to both bicuculline and baclofen (GABA-A and GABA-B antagonists). 
Additional roles for GABAergic neurotransmission include:
Involvement in mood disorders and psychiatric disorders. For example, GABA agonists are effective antidepressant and antimanic agents, suggesting a GABA deficit.
Serving as a developmental signal (see above).
Mediating synaptic inhibition.
Inhibitory role in motor output structures like the substantia nigra. 
Inhibiting DNA synthesis.
Sources:
Petty, F. 1995. GABA and Mood Disorders: A brief review and hypothesis. Journal of Affective Disorders. 34 (4): 275-281. doi:10.1016/0165-0327(95)00025-I
Owens, D.F. & Kriegstein A.R. 2002. Is there more to GABA than synaptic inhibition? Nature Reviews Neuroscience. 3:715-727. doi:10.1038/nrn919
Watanabe, M., et al. 2002. GABA and GABA Receptors in the Central Nervous Systems and Other Organs. International Review of Cytology. 213:1-47.
doi:10.1016/S0074-7696(02)13011-7

 

GABA: The main inhibitory neurotransmitter in the central nervous system. 

  • GABA is considered part of the small neurotransmitter molecules (like acetylcholine and glutamate) and is synthesized directly in the axon terminal, near the release site.
  • GABA, along with its signaling components, receptors, enzymes, transporters, and such are present early in development. 
  • GABA is a multifunctional molecules with different situational roles throughout development. Functions include: influencing neural migration, acting as a neurotrophic factor and facilitating neurite extension/maturation. 
  • Glutamate is the precursor of GABA. Glutamate is converted into GABA by a decarboxylation reaction catalyzed by glutamic acid decarboxylase (GAD), a rate limiting enzyme in GABA synthesis that requires the cofactor pyridoxal phosphate (PLP).
  • Like glutamate, GABAergic neurotransmission relies on different kinds of receptors (i.e. ionotropic vs. metabotropic) that are characterized by pharmacological differences.
  • There are 3 GABA receptors: GABA-A, GABA-B, GABA-C.
  • GABA-A and GABA-C receptors are ionotropic and mediate fast (inhibitory) GABA responses by triggering calcium channel openings. In other words, they are ligand-gated calcium channels. Bicuculline is a GABA-A receptor antagonist. 
  • GABA-A receptors are classified according to their corresponding amino acid sequence. Additionally, many receptor subunits have been found and each has a unique distribution in the brain. The diversity of GABA-A receptor subtypes are thought to highlight their great importance in the regulation of brain excitability. GABA-A receptors also include binding sites for other clinically relevant drugs (i.e. benzodiazepines).
  • GABA-B receptors are metabotropic receptors that are a part of the g-protein coupled receptor (GPCRs) family and mediate slower GABA responses by activating G-proteins to influence second messenger systems. These mostly regulate calcium and potassium channel openings to mediate the long-term inhibitory actions of GABA. Moreover, GABA-B receptors are present pre and post-synaptically. Baclofen is a GABA-B receptor antagonist. 
  • GABA-B receptors play an important role in long term inhibition of synaptic transmission. GABA-B autoreceptors control the release of GABA while GABA-B heteroreceptors control the release of glutamate, noradrenaline, dopamine, substance P and others. Finally, GABA-B receptor distribution is different than GABA-A receptor distribution in the brain. 
  • GABA-C receptors have a similar structure (pentameric chloride sensitive channels) and composition (different subunits) similar to GABA-A receptors, but vary in their kinetic and pharmacological properties. However, they have greater sensitivity to GABA compared to GABA-A receptors. GABA-C receptors are insensitive to both bicuculline and baclofen (GABA-A and GABA-B antagonists). 

Additional roles for GABAergic neurotransmission include:

  1. Involvement in mood disorders and psychiatric disorders. For example, GABA agonists are effective antidepressant and antimanic agents, suggesting a GABA deficit.
  2. Serving as a developmental signal (see above).
  3. Mediating synaptic inhibition.
  4. Inhibitory role in motor output structures like the substantia nigra. 
  5. Inhibiting DNA synthesis.

Sources:

Petty, F. 1995. GABA and Mood Disorders: A brief review and hypothesis. Journal of Affective Disorders. 34 (4): 275-281. doi:10.1016/0165-0327(95)00025-I

Owens, D.F. & Kriegstein A.R. 2002. Is there more to GABA than synaptic inhibition? Nature Reviews Neuroscience. 3:715-727. doi:10.1038/nrn919

Watanabe, M., et al. 2002. GABA and GABA Receptors in the Central Nervous Systems and Other Organs. International Review of Cytology. 213:1-47.

doi:10.1016/S0074-7696(02)13011-7


 

  1. patronsaintofthedamned reblogged this from houseofmind
  2. debsvallejo reblogged this from houseofmind
  3. stephtronic reblogged this from houseofmind
  4. becomingestel reblogged this from houseofmind and added:
    an effective way to get some studying done while tumblring ;)
  5. talkingshrimp reblogged this from houseofmind
  6. xxxxxgbfpxxxxx reblogged this from houseofmind
  7. beeeface reblogged this from interferon-gamma
  8. arjunasekai reblogged this from houseofmind
  9. interferon-gamma reblogged this from houseofmind
  10. julieuh reblogged this from houseofmind
  11. w3fa reblogged this from houseofmind
  12. tziganeheart reblogged this from houseofmind
  13. wan-n-der reblogged this from houseofmind
  14. cannabalistic-muffin reblogged this from houseofmind
  15. questionall reblogged this from houseofmind
  16. suerreal-sp reblogged this from houseofmind
  17. houseofmind posted this