2/14/19 1 How does GABA inhibit neurons? Dr. Amanda Freeman + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + ++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
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2/14/19
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HowdoesGABAinhibit
neurons?
Dr.AmandaFreeman
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DifferentTypesofGABAReceptors
GABAA GABAB
Insid
ene
uron
Outsid
ene
uron
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GABAA
Chloride(Cl-)-GABA
DifferentTypesofGABAReceptors
Insid
ene
uron
Outsid
ene
uron
GABAA
-
GABA
Insid
ene
uron
Outsid
ene
uron
Importanttargetfor- Tranquilizers- Anesthetics- Anticonvulsants
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GABAB
DifferentTypesofGABAReceptors
+Potassium(K+)
Insid
ene
uron
Outsid
ene
uron
GABAA
-
GABAGABA
GABAB
+
Insid
ene
uron
Outsid
ene
uron
Importanttargetfor- MuscleRelaxants- Antiepileptics
GABA
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GABAA GABAB
Young&Chu(1990)DrugDevelopmentResearch.21:161-167.
GABAA Receptor
From the side From the top
α
α β
βγ
α
α β
βγ
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GABAA ReceptorGABAbindingsites
From the side From the top
α
α β
βγ
α
α β
βγ
GABAA ReceptorEthanolandvolatileanestheticbindingsites
From the side From the top
α
α β
βγ
α
α β
βγ
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GABAA ReceptorBenzodiazepinebindingsite
From the side From the top
α
α β
βγ
α
α β
βγ
GABAAreceptorsubtype
PercentageofallGABAA receptors
Function
α1(α1β2γ2)
60%
AnestheticsSedation*Amnesia*
Anticonvulsant*
α2 15-20% Anxiolytic*
α3 10-15% Musclerelaxation*Anxiolytic*
α5 <5% Learning andMemory
*EffectsofBenzodiazepines
BaseduponNutt(2006)JournalofClinicalSleepMedicine,2(2):S7-S11.
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Pirkeretal.(2000)Neuroscience.101(4):815-850.
GABAAreceptorsubunits
WhatdoesGABAhavetodo
withsleep?
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HistamineSerotonin
NorepinephrineAcetylcholine
Hypocretin/Orexin
WakePromoting
GABAFromVentrolateralPreopticArea(VLPO)
SleepPromoting
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(2012)ScienceTranslationalMedicine4(161):161ra151
WakeHistamineSerotonin
NorepinephrineAcetylcholine
Hypocretin/Orexin
SleepGABA
GABA
Chloride
GABA
GABA
Chloride
GABA-relatedHypersomnia
GABA
Chloride
GABA-relatedHypersomnia+Flumazenil
GABA
Chloride
Benzodiazepine
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