BIDN, a bicyclic dinitrile convulsant, selectively blocks GABA-gated Cl- channels

BIDN (3,3-bis(trifluoromethyl)bicyclo[2,2,1]heptane-2,2-dicarbonitrile) at 10-5 M blocked GABA-induced inhibitory postsynaptic potentials (IPSPs) recorded from an identified, giant interneurone (G12) of the cockroach (Periplaneta americana). The same concentration of this bicyclic dinitrile also blocked Clmediated responses of G12 to GABA applied by pressure microinjection into the terminal abdominal ganglion neuropile containing dendrites of G12. BIDN (10-5 M) was without effect on a response of G12 to GABA known to be mediated by a GABA(B) type receptor. In studies of the cell body of an identified motor neurone, the fast coxal depressor (D(f)) in the cockroach metathoracic ganglion, BIDN (10-5 M) blocked reversibly an extrasynaptic GABA-gated Cl- channel, but not an extrasynaptic L-glutamate- gated Cl- channel. Glycine-gated Cl- channels observed when rat brain messenger RNA was expressed in Xenopus laevis oocytes were unaffected by BIDN at concentrations up to 10-4 M, whereas this same concentration of BIDN completely blocked GABA-gated Cl- responses recorded from the same preparations. Unlike picrotoxin, which antagonises a variety of ligand-gated Cl- channels, to date BIDN has been found to block only Cl- channels gated by GABA, both in insect and vertebrate preparations.