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

The effects of virol A (VA), a toxic component of Cicuta virosa (water heml ock), on the GABA-induced Cl- current (I-GABA) in acutely dissociated rat h ippocampal CAI neurons were investigated using whole-cell patch-clamp techn iques. VA reversibly reduced I-GABA and the muscimol (Mus)-induced current (I-Mus) in a concentration-dependent manner. The IC50 values for VA against I-GABA and I-Mus were 9.6X10(-7) and 9.8X10(-7) M, respectively. VA shifte d the EC50 value of I-GABA from 6.5x10(-6) to 2.1X10(-5) M, whereas it had no effect on the maximum response, thereby suggesting that VA inhibited I-G ABA in a competitive manner. VA had no apparent effect on current-voltage r elationships for I-GABA thus indicating the lack of voltage-dependency. On the other hand, application of VA (10(-6) M) did not additionally reduce th e I-GABA suppressed by >10(-5) M picrotoxin. VA but not bicuculline acceler ated the decay phase of I-GABA as, was seen with picrotoxin. Moreover, pre- application of 10(-5) M VA reduced I-GABA. VA did not inhibit that induced by glycine (10(-4) M). These results indicate that VA inhibits I-GABA by ac ting both on the GABA agonist site and on the CI channel of the GABA, recep tor-channel complex. VA is a structurally novel type of compound that selec tively inhibits the GABA(A) receptor-Cl- channel complexes in mammalian cen tral nervous system neurons. (C) 2001 Elsevier Science B.V. All rights rese rved.