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.
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008874:Midazolam; D009433:Neural Inhibition / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D007473:Ion Channels; D001569:Benzodiazepines; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D008874:Midazolam; D011188:Potassium; D002118:Calcium