Abstract
The action of gamma-aminobutyric acid (GABA) and the GABAA-receptor agonists muscimol, isoguvacine and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol (THIP) were studied at the single-channel level in outside-out membrane patches from cultured chick cerebral neurons. All agonists activated channels with multiple-conductance states. The main-state conductance activated by all agonists had a value around 26 pS in symmetrical TRIS/Cl solutions. Subconductance states of around 13 pS and 18 pS were seen with application of each agonist. Muscimol and isoguvacine tended preferentially to activate subconductance states. Gating by all agonists was complex. Open-time distributions for main-state activity gated by GABA, isoguvacine and THIP were best described by the sum of two exponential curves with similar time constants. Muscimol-gated activity was best described by the sum of three exponentials indicating the presence of an additional longer open state. These results indicate that certain GABAA-receptor agonists are capable of preferentially activating subconductance states.
MeSH Terms
Analgesics/pharmacology
Animals
Cells, Cultured
Cerebral Cortex/cytology,drug effects,physiology
Chick Embryo
Chlorides
Electric Conductivity/drug effects,physiology
Ion Channel Gating/drug effects,physiology
Ion Channels/metabolism,physiology,ultrastructure
Isonicotinic Acids/pharmacology
Isoxazoles/pharmacology
Muscimol/pharmacology
Neurons/drug effects,physiology,ultrastructure
gamma-Aminobutyric Acid/pharmacology
Chemicals
Analgesics
Chlorides
Ion Channels
Isonicotinic Acids
Isoxazoles
Muscimol
gamma-Aminobutyric Acid
gaboxadol
isoguvacine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mistry D K
Neurobiology Research Center, University of Alabama, Birmingham 35294.
Hablitz J J
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