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Enhancement by propofol of the gamma-aminobutyric acidA response in dissociated hippocampal pyramidal neurons of the rat.

Abstract：

BACKGROUND:Activation of the gamma-aminobutyric acidA (GABAA) receptor-ionophore complex has been reported as a possible molecular mechanism of the anesthetic action of propofol. Augmentation of GABA-induced inhibitory transmission has also been suggested as a mechanism. Because data describing this latter mechanism in mammalian neurons are few, we have examined the effects of propofol on the GABA response in central neurons of the rat. METHODS:Hippocampal pyramidal neurons were dissociated after enzyme treatment of the rat brain slices. The neurons were voltage-clamped with the whole cell configuration of the patch clamp technique. Neurotransmitters and drugs were applied using the "Y-tube" method, which exchanges the extracellular solutions around the neuron within 10-20 ms and makes it possible to obtain the peak response before desensitization develops. RESULTS:In pyramidal neurons voltage-clamped at -60 mV, GABA induced an inward current. Propofol (10(-6) M) augmented the current and shifted the concentration-response curve for GABA to the left without affecting the maximum response. A low concentration of the anesthetic (10(-6) M) reduced the dissociation constant for GABA from 8.2 x 10(-6) to 4.2 x 10(-6) M without a significant effect on the Hill coefficient. Coapplication of propofol at a higher concentration (5 x 10(-6) M) also shifted the GABA dose-response curve to the left, reducing the dissociation constant to 2.8 x 10(-6) M. Potentiation by propofol was not associated with a change in the reversal potential for the GABA response and was not voltage-dependent. The inhibitory glycine response was not affected by propofol (10(-6) M or 5 x 10(-6) M). CONCLUSIONS:Propofol at clinically relevant concentrations enhances the inhibitory GABAA receptor-mediated response in mammalian central neurons. The enhancement may result in reduced excitability of the neuronal network and may, consequently, contribute to the anesthetic action of the agent.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Hara M,Kai Y,Ikemoto Y

doi

10.1097/00000542-199410000-00026

subject

Has Abstract

pub_date

1994-10-01 00:00:00

pages

988-94

issue

eissn

0003-3022

issn

1528-1175

journal_volume

pub_type

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Enhancement by propofol of the gamma-aminobutyric acidA response in dissociated hippocampal pyramidal neurons of the rat.