2003B03 Outline GABA’s role as a neurotransmitter and indicate how its actions
may be modified by pharmacological agents.

 

List:

·      GABA

·      GABA-A

·      GABA-B

·      Drugs

 

GABA: (γ-aminobutyric acid)

Type of neurotransmitter

·   Inhibitory

Location

·   Brain > spinal cord > peripheral sites

·   Especially hippocampus, other limbic structures, brainstem

Production

·   Glutamic acid -> GABA

·   Enzyme: glutamic acid decarboxylase

·   Cofactor: vitamin B6

Degradation

·   GABA -> glutamate or succinate

·   Enzyme: GABA transaminase (inhibited by some anticonvulsants)

 

GABA-A receptor:

Diagramme

Structure

·   Pentameric ligand-gated ion channel

·   α1β1α2β2γ

Location

·   Mostly post-synaptic

Activation

·   ↑Cl- conductance, prevention of action potential

·   (no hyperpolarization since RMP -70mV, Cl- Nernst potential -65mV)

·   Rapid onset and offset (milliseconds)

Subtypes

·   α1: sedation, amnesia, anticonvulsant

·   α2, α3: muscle relaxation, anxiolysis

 

GABA-B receptor:

Type

·   Metabotropic G protein coupled receptor

Location

·   Mostly pre-synaptic

Activation

·   ↑K+ efflux, hyperpolarization, ↓action potential

·   Slower onset (seconds) and offset

 

Drugs at GABA-A receptor:

Benzodiazepines

·   e.g. midazolam

·   Binds BDZ site at α-γ interface

·   ↑probability of adopting active conformation once GABA bound

·   Note flumazenil competitive antagonist at same site

Propofol

Thiopentone

Volatile agents

·   Bind A and/or B subunit

·   ↓rate of dissociation of GABA from its receptor

Baclofen

·   Derivative of GABA

·   Active at GABA-A

Gamma hydroxybutyrate

·   Precursor to GABA

·   Weak agonist at GABA-A

Alcohol

Etomidate

·   Unknown

 

 

Feedback welcome at ketaminenightmares@gmail.com