Convulsant gamma-butyrolactones block GABA currents in cultured chick spinal cord neurons.
The gamma-aminobutyric acid (GABA) inhibiting properties of the beta-substituted gamma-butyrolactone convulsant, beta-isopropyl-gamma-butyrolactone (beta IPGBL), were studied using gigaseal recording techniques in cultured chick spinal cord neurons. beta IPGBL produced a dose-dependent inhibition of GABA currents with half maximal effect at 92 microM. The effects of beta IPGBL were immediate and completely reversible within minutes after exposure. The inhibition by beta IPGBL showed mixed competitive and non-competitive features with little voltage-dependence. beta IPGBL did not alter the GABA reversal potential nor the degree of GABA desensitization. At a single-channel level, beta IPGBL markedly diminished the opening of GABA channels and decreased the mean channel open time by 30-40% without affecting the amplitude of the single-channel current.
Zorumski
C F
CF
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Yang
J
J
Baker
K
K
Covey
D F
DF
Clifford
D B
DB
D015107:4-Butyrolactone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D005663:Furans / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015107:4-Butyrolactone; D005663:Furans; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid