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Mechanisms of etomidate potentiation of GABAA receptor-gated currents in cultured postnatal hippocampal neurons.

Abstract：

:The effect of etomidate, an imidazole general anesthetic, on GABAA receptor function was studied in cultured hippocampal neurons. At a clinically relevant concentration of 4.1 microM, etomidate shifts the GABA dose response to the left (ED50 shift from 10.2 to 5.2 microM), with no change in the maximum current evoked by saturating concentrations of GABA. At a higher concentration of 82 microM, etomidate directly induces current in the absence of GABA. Etomidate selectively increases the amplitude and prolongs the duration of miniature inhibitory postsynaptic currents without significant effects on miniature inhibitory postsynaptic currents. The combined effects of etomidate on miniature inhibitory postsynaptic current amplitude and duration enhance the total charge transfer by 280% during a spontaneous synaptic event. Analysis of single channels opened by GABA indicates that 8.2 microM etomidate increases the probability of channels being open 13-fold and increases the effective channel open time two-fold. Given the present understanding of central inhibitory synapses, the effect of etomidate on channel kinetics is most likely to be the predominant mechanism which influences the synaptic function. In addition, etomidate, through its modulation of both channel kinetics and open probability, is likely to have a large impact on extrasynaptic GABAA receptor function.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Yang J,Uchida I

doi

10.1016/0306-4522(96)00018-8

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

69-78

issue

1

eissn

0306-4522

issn

1873-7544

pii

0306452296000188

journal_volume

73

pub_type

杂志文章

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