A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons.
Whole-cell patch-clamp recordings were made from cultured rat hippocampal neurons to examine the effects of the steroidal general anesthetic alphaxalone (3 alpha-hydroxy 5 alpha-pregnane 11,20-dione) on responses to pharmacologically applied and physiologically released GABA. At low micromolar concentrations in the anesthetic range, alphaxalone potentiated Cl- conductance responses elicited by GABA and also prolonged evoked GABA-mediated postsynaptic potentials. Under voltage clamp at -40 mV, rapid outwardly directed synaptic currents were evoked that decayed with single exponential kinetics; mean decay time constant was 24 msec at room temperature. Alphaxalone prolonged the decay of these inhibitory postsynaptic currents by 5- to 8-fold, with no increase in peak amplitude or change in growth time. This substantial prolongation of GABA-mediated inhibitory synaptic conductance at clinically effective concentrations may contribute significantly to the anesthetic activity of alphaxalone.
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology; D004553:Electric Conductivity; D006624:Hippocampus / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D011277:Pregnanediones / Q000494:pharmacology*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000777:Anesthetics; D002712:Chlorides; D011277:Pregnanediones; D005680:gamma-Aminobutyric Acid; C006477:alphaxalone