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

Abstract

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 Cl −-mediated 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.