Virol A, a toxic trans-polyacetylenic alcohol of Cicuta virosa, selectively inhibits the GABA-induced Cl- current in acutely dissociated rat hippocampal CA1 neurons

Koji Uwai, Katsuyo Ohashi, Yoshiaki Takaya, Yoshiteru Oshima, Ken ichi Furukawa, Kanato Yamagata, Tomohiro Omura, Shigeru Okuyama

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13 Citations (Scopus)

Abstract

The effects of virol A (VA), a toxic component of Cicuta virosa (water hemlock), on the GABA-induced Cl- current (IGABA) in acutely dissociated rat hippocampal CA1 neurons were investigated using whole-cell patch-clamp techniques. VA reversibly reduced IGABA and the muscimol (Mus)-induced current (IMus) in a concentration-dependent manner. The IC50 values for VA against IGABA and IMus were 9.6×10-7 and 9.8×10-7 M, respectively. VA shifted the EC50 value of IGABA from 6.5×10-6 to 2.1×10-5 M, whereas it had no effect on the maximum response, thereby suggesting that VA inhibited IGABA in a competitive manner. VA had no apparent effect on current-voltage relationships for IGABA, thus indicating the lack of voltage-dependency. On the other hand, application of VA (10-6 M) did not additionally reduce the IGABA suppressed by >10-5 M picrotoxin. VA but not bicuculline accelerated the decay phase of IGABA, as was seen with picrotoxin. Moreover, pre-application of 10-5 M VA reduced IGABA. VA did not inhibit that induced by glycine (10-4 M). These results indicate that VA inhibits IGABA by acting both on the GABA agonist site and on the Cl- channel of the GABAA receptor-channel complex. VA is a structurally novel type of compound that selectively inhibits the GABAA receptor-Cl- channel complexes in mammalian central nervous system neurons.

Original languageEnglish
Pages (from-to)174-180
Number of pages7
JournalBrain research
Volume889
Issue number1-2
DOIs
Publication statusPublished - 2001 Jan 19

Keywords

  • GABA receptor
  • Hippocampal neuron
  • Virol A

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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