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Journal of Neuroscience, Vol 7, 604-609, Copyright © 1987 by Society for Neuroscience
A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons
NL Harrison, S Vicini and JL Barker
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.
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