anxiety/sedation/depression

Question 1

outline GABA synthesis and metabolism in pre-synaptic nerve terminal (typically localised, short axon interneuron in brain, but also in long descending strionigral tract - opposite of ascending nigrostriatal tract for dopamine)

Answer 1

synthesised from glutamate precursor by GAD and released; uptaken and metabolised to SSA by GABA-T

Question 2

outline GABA metabolism by glial cells

Answer 2

uptaken and metabolised to SSA by GABA-T

Question 3

what is GABA receptor on post-synaptic cell

Answer 3

GABA-A (Cl- ionophore type 1 receptor)

Question 4

function of GABA autoreceptors (GABA-B) on pre-synaptic nerve terminals

Answer 4

regulate release of GABA, so if too much release it damps down release (inhibitory)

Question 5

2 stages of GABA metabolism to succinic acid (TCA cycle), including enzymes

Answer 5

GABA -> succinic semialdehyde by GABA-T -> succinic acid by SSDH

Question 6

where does metabolism of GABA occur (location of enzymes)

Answer 6

mitochondria, although GAD (synthesis) is cytoplasmic

Question 7

outcome of inhibitition of GABA metabolism

Answer 7

large increase in brain GABA

Question 8

2 drugs which inhibit GABA metabolism which are used in treatment of epilepsy, and mechanisms of action

Answer 8

sodium valproate (inhibits GABA-T weakly and SSDH, and inhibits voltage-gated Na+ channels so anti-convulsant), vigabatrin (GABA-T suicide inhibitor as binds covalently)

Question 9

describe GABA-A receptor complex (post-synaptic)

Answer 9

4 proteins: Cl- channel protein in centre, with GABA receptor protein (associated with GABA modulin), barbiturate receptor protein and benzodiazepine receptor protein on outside

Question 10

what is a GABA competetive antagonist

Answer 10

bicuculline

Question 11

what is a benzodiazepine competitive antagonist

Answer 11

flumazenil

Question 12

effect of GABA binding to GABA-A receptor (on GABA receptor protein)

Answer 12

opens Cl- protein rapidly within GABA-A receptor when GABA binds -> Cl- flows into post-synaptic cell -> hyperpolarises membrane so more difficult to excite

Question 13

effects of benzodiazepines binding (allosteric) to GABA-A receptor (benzodiazepine receptor protein)

Answer 13

enhanced Cl- influx into post-synaptic cell, binding of GABA is enhanced (increased affinity), reciprocated response to enhance benzodiazepine binding

Question 14

effects of barbiturates binding (allosteric) to GABA-A receptor (on barbiturate receptor protein)

Answer 14

enhance normal action of GABA, enhance affinity of GABA binding (no change in barbiturate binding), at higher concentration of barbiturate can get additional direct influx of Cl- through Cl- channel