Neuroscience 2004 Abstract
| Presentation Number: | 844.4 |
|---|---|
| Abstract Title: | Etomidate sensitivity is reduced in hippocampal pyramidal neurons from GABA<sub>A</sub> receptor α5 subunit null mutant mice. |
| Authors: |
Orser, B. A.*1,2,3
; Elliott, E. M.1
; MacDonald, J. F.1
; Wafford, K. A.4
1Physiology, Univ. of Toronto, Toronto, Canada 2Insitute of Med. Sci., Univ. of Toronto, Toronto, Canada 3Anesthesia, Univ. of Toronto, Toronto, Canada 4United Kingdom, Med Sci Bldg, M5S1A8, |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Ligand Gated Ion Channels -- GABAa receptors |
| Session: |
844. GABAA: Pharmacosteroidal and Steroidal Regulation Poster |
| Presentation Time: | Wednesday, October 27, 2004 11:00 AM-12:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # H1 |
| Keywords: | memory, amnesia, anesthesia, GABAergic |
It is widely believed that the general anesthetic, etomidate, depresses neuronal excitability by allosterically modulating postsynaptic GABAA receptors (GABAARs) and increasing inhibitory synaptic transmission. Hippocampal pyramidal neurons generate two forms of GABAergic inhibition including transient postsynaptic currents and a persistent “tonic” conductance. We recently showed that GABAARs containing the α5 subunit (α5GABAARs) generate the tonic but not synaptic currents in murine CA1 pyramidal neurons (PNAS 101:3662). Further, low concentrations of etomidate selectively enhance the tonic but not synaptic currents in hippocampal neurons (SFN Abstract 2003 #571.2). To test the hypothesis that etomidate increases the tonic current by modulating α5GABAARs, we examined the effects of etomidate in neurons from wildtype (α5+/+) and α5 subunit null mutant mice (α5-/-). Hippocampal neurons from postnatal mice (P1) were grown in dissociated cultures and examined using standard whole-cell recording methods (Vm -60 mV). The α5+/+ neurons exhibited a greater sensitivity to etomidate compared to α5-/- neurons (0.1 µM: 30±14 pA vs 4±2 pA, n=7, p<0.01; 1 µM , 96±21 pA vs 14±3 pA, n=7, p<0.01). Since α5GABAARs have been implicated in learning and memory processes (J Neurosci 22:5572), our results suggest that increased tonic GABAergic inhibition in hippocampal neurons may contribute to behavioural effects of low doses of etomidate, notably amnesia.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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