Low-dose benzodiazepine neuronal inhibition: enhanced Ca2+-mediated K+-conductance.

The water-soluble inhibitory benzodiazepine, midazolam, was applied in low nanomolar concentrations to CA1 hippocampal neurons in vitro, recorded intracellularly. The drug caused a long-lasting hyperpolarization and moderate conductance increase, which persisted with TTX-induced synaptic blockade or with intracellular injection of Cl- ions, but not in zero Ca2+ perfusate. Calcium spikes elicited in the presence of TTX were enhanced by midazolam. It was concluded that these low nanomolar concentrations, which did not enhance GABA actions, inhibited by augmenting Ca2+ mediated K+-conductance.