Comparison of the GABAergic currents associated with midazolam and propofol in rat hippocampal neurons.

Abstract

gamma-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter, activates persistent low amplitude tonic currents in several brain regions, in addition to conventional synaptic currents. Tonic conductance is highly sensitive to low concentrations of volatile anesthetics and therefore might contribute to amnestic properties. We compared the properties of GABAergic tonic currents mediated by sedative-amnestic midazolam and anesthetic propofol in rat hippocampal neurons. Patch clamp techniques were used to characterize the GABAergic currents recorded in CA1 pyramidal neurons in rat hippocampal slices. The amplitude of the tonic currents and the decay of miniature inhibitory postsynaptic currents (mIPSCs) were measured after administration of midazolam or propofol. Both midazolam and propofol caused concentration dependent increases in the tonic currents. The enhancement of the tonic currents by midazolam concentrations of greater than 0.5 microM caused no further increase in current amplitude. Propofol continued to increase with concentrations over the range tested (0.1-10 microM). Low concentrations of midazolam 0.01 microM and propofol 0.5 microM selectively enhanced the tonic currents but failed to alter mIPSCs. Low concentrations of midazolam and propofol selectively enhanced the tonic currents but not synaptic currents of rat hippocampal pyramidal neurons. Unlike midazolam, the response to propofol did not become saturated and had a greater effect on the tonic currents.