Journal of Neuroscience, Vol 6, 3161-3168, Copyright © 1986 by Society for Neuroscience
Facilitatory action of etomidate and pentobarbital on recurrent inhibition in rat hippocampal pyramidal neurons
WR Proctor, M Mynlieff and TV Dunwiddie
Biochemical studies have shown that the non-barbiturate anesthetic
etomidate can interact in a stereoselective, barbiturate-like fashion with
the GABA/benzodiazepine receptor complex, enhancing both benzodiazepine and
GABA binding, but its electrophysiological effects upon the mammalian CNS
are largely unknown. The present investigations were designed to
characterize the electrophysiological effects of etomidate on the recurrent
GABAergic inhibitory pathway in the CA1 region of the rat in vitro
hippocampal slice and to compare the actions of etomidate to those of
pentobarbital. Electrical stimulation of the alveus elicited a biphasic
hyperpolarizing response, consisting of an initial bicuculline-sensitive
GABAergic IPSP. This was followed by a second component, termed the late
hyperpolarizing potential (LHP), which is thought to reflect an increase in
potassium conductance. Both pentobarbital (100 microM) and (+)-etomidate
(10 microM) markedly increased the duration of the initial GABA-mediated
IPSP, and frequently increased its amplitude as well. However, no
significant effects of either of these drugs were observed on the LHP.
Together with previous biochemical findings, our data suggest that the
depressant effects of etomidate and barbiturates on the nervous system may
reflect a common action upon a stereoselective receptor site intimately
associated with bicuculline-sensitive GABA receptors and the chloride ion
channel.
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