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A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons



A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons



Journal of Neuroscience 7(2): 604-609



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; when 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.

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Accession: 004630620

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PMID: 3819824


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