GABA

what is GABA

• widely distributed AA NT

  • primarily functions as a NT

  • ONLY inhibitory

  • helps keep brain in balance

what can blocking GABA do

• lead to seizures, convulsions, death

what is it co-released with

• ACh, DA, or glutamate

  • GABA and Glu released together for fine tuning

what terminals use GABA

• 10-40% in cerebral cortex, hippocampus, and substantia nigra

what is it synthesized from?

• glutamate

  • therefore, from glutamine

what is it broken down by?

• GABA aminotransferase

  • GABA-T

what is the pathway for GABA

• glutamate

  • GAD — glutamic acid decarboxylase

• GABA

draw out the pathway

• glutamate — (GAD) → GABA packed in vesicles via vesicular GABA transporter → GABA secreted from vesicle

• GABA Rs bind GABA

• GAT-1,2,3 — on astrocyte

  • GABA → glutamate — (glutamine synthetase) → glutamine

  • glutamine transporters take glutamine from astrocytes to nerve terminal

• GAT-1 — on nerve terminal

what does GABA-T do? what is the metabolite

• breaks down GABA into glutamate and succinate in neurons and astrocytes

• succinate is considered a GABA metabolite and can be used in the Krebs cycle as an energy source

VGAT

• vesicular GABA transporters

• puts GABA into vesicles

• AKA VIAAT

  • vesicular inhibitory AA transporters

reuptake

GAT 1, 2, 3

GAT1 loc and knockouts and fx

• found primarily on presyn terminals and astrocytes

• widespread, cerebral cortex

• knockouts demonstrate anxiety/panic like behaviors

GAT2 loc and knockouts and fx

• found primarily in liver and kidneys

• unknown role but transports taurine

GAT3 loc and knockouts and fx

• found only on astrocytes

• widespread, brainstem/hindbrain

describe the GABA pathways with ACh, DA, Glu

GABA-A

• ionotropic (controls Cl- channel)

• can sometimes dysfunction and cause Cl- outflow

  • some forms of epilepsy are linked to mutations

GABA-B

• metabotropic (opens K+ channels)

• also found as autoreceptors and inhibit Ca2+ channel opening

baclofen

• agonist of GABA-B

• muscle relaxant.antispastic agent

GABA-A drugs

• muscimol (in mushrooms)

  • competitive agonist

  • macroscopia — the perception that objects are larger than they really are

• benzodiazepines

  • xanax, ativan, valium

  • non-competitive agonist

GABA-A drugs

• withdrawal can be deadly

• overdose is easy

what else releases GABA?

• beta-cells in the pancreas release GABA with insulin to inhibit glucagon release

• GABAergic system in testes

• found in plants indicating they may have cellular signaling capabilities

what did GABA inc the conversion of?

• the conversion of serotonin into melatonin, suggesting a role in circadian rhythms