These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Physiological regulation of the picrotoxin receptor by gamma-butyrolactones and gamma-thiobutyrolactones in cultured hippocampal neurons.
    Author: Holland KD, Ferrendelli JA, Covey DF, Rothman SM.
    Journal: J Neurosci; 1990 Jun; 10(6):1719-27. PubMed ID: 2355246.
    Abstract:
    We examined the effects of alkyl-substituted gamma-butyrolactones (GBLs), and gamma-thiobutyrolactones (TBLs) on GABA currents in cultured, voltage-clamped rat hippocampal neurons. Convulsant GBLs and TBLs reversiby diminished GABA responses in a concentration-dependent manner. beta-Ethyl-beta-methyl GBL (beta-EMGBL) completely abolished GABA responses at 3 mM (IC(50)390 microM), while TBL and beta-ethyl-beta-methyl TBL (beta-EMTBL)-induced inhibition of GABA currents was incomplete, saturating at about 50% of control at 300 microM and 10 mM for beta-EMTBL and TBL, respectively. beta-EMGBL and beta-EMTBL both increased the rate of decay of inhibitory post-synaptic currents (IPSCs) and beta-EMGBL also decreased IPSC peak amplitude. In contrast, the anticonvulsant alpha-ethyl-alpha-methyl TBL (alpha-EMTBL) potentiated GABA currents at all GABA concentrations tested; maximal potentiation was 190% of control at 1 mM alpha-EMTBL (EC50 102 microM). Another anticonvulsant alpha-ethyl-alpha-methyl GBL (alpha-EMGBL), potentiated responses to low (0.5 microM) but not high (greater than or equal to 10 microM) GABA. It also blocked the inhibitory effects of picrotoxin and beta-EMGBL and the facilitative effect of alpha-EMTBL on responses to 30 microM GABA. alpha-EMGBL did not interfere with other agents which augment GABA currents. Both alpha-EMTBL and alpha-EMGBL decreased the rate of IPSC decay without altering IPSC peak amplitude. None of these compounds had any direct membrane effects. We propose that beta-alkyl GBLs diminish GABA currents, and therefore, we hypothesize that these compounds are picrotoxin receptor agonists. beta-Alkyl TBLs partially diminish GABA currents and may be partial agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
    [Abstract] [Full Text] [Related] [New Search]