Alpha-substituted thiobutyrolactones potentiate GABA currents in voltage-clamped chick spinal cord neurons.
The effect of the experimental anticonvulsant, alpha-ethyl,methyl thiobutyrolactone (alpha-EMTBL), on gamma-aminobutyric acid (GABA) currents was examined in cultured chick spinal cord neurons using gigaseal recording techniques. alpha-EMTBL potentiated GABA responses in a dose-dependent fashion with half-maximal effect at 7 microM. alpha-EMTBL also augmented the response to maximal doses of GABA. In competition experiments, alpha-EMTBL relieved the block of GABA currents produced by saturating concentrations of picrotoxinin whereas diazepam and phenobarbital did not. At a single channel level, alpha-EMTBL increased the probability of opening GABA channels without significantly altering the mean channel open time or the single channel conductance. These results indicate that alpha-EMTBL potentiates GABA responses and has properties which distinguish it from benzodiazepines or barbiturates.
Baker
K
K
Department of Anatomy, Washington University School of Medicine, St. Louis, MO 63110.
Yang
J
J
Covey
D F
DF
Clifford
D B
DB
Zorumski
C F
CF
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003975:Diazepam / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015107:4-Butyrolactone; D000927:Anticonvulsants; D003975:Diazepam; D005663:Furans; D007473:Ion Channels; D010634:Phenobarbital; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C051894:alpha-ethyl, alpha-methyl-thiobutyrolactone