Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture.

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Abstract
Chlordiazepoxide (CDPX) and other benzodiazepines potentiate submaximal increases in membrane conductance produced by GABA (gGABA) in chick spinal cord and dorsal root ganglion neurons maintained in cell culture. The maximum gGABA was not increased and the GABA reversal potential was not altered. The potentiation is selective in that responses to glycine and other amino acids are not affected. The effect of CDPX was evident immediately after application (by pressure ejection), and the potentiation did not desensitize over the course of several hours. Potentiation of submaximal GABA conductance was CDPX dose-dependent between concentrations of 10-7 and 10-3 M, with an ED50 of 17 .mu.M. The CDPX dose-response curve did not exhibit cooperativity: the Hill slope was 1.00. In the presence of CDPX, the GABA ED50 was lowered from 17 to 8 .mu.M. The entire GABA dose-response curve was shifted in a parallel fashion without a change in cooperativity. CDPX-induced potentiation is probably due to an effect on the target cell membrane rather than to an effect on GABA release or uptake. Since CDPX is not a GABA agonist at potentiating concentrations, it may act at a locus other than the GABA binding site to modulate GABA binding, or the coupling between GABA binding and increase in membrane permeability.