Article date: July 1994
By: A.C. Hall, W.R. Lieb, N.P. Franks, in Volume 112, Issue 3, pages 906-910
Acutely dissociated cerebellar Purkinje neurones from 8–14 day old rats were studied under voltage clamp in the whole‐cell patch‐clamp configuration. Cl− currents induced by bath application of γ‐aminobutyric acid (GABA) were measured (using symmetrical Cl− solutions) at both low (2 μm) non‐desensitizing and high (300 μm) desensitizing concentrations of GABA.
At 2 μm GABA, the bicuculline‐sensitive Cl− currents were potentiated by racemic isoflurane and both of its optical isomers. Isoflurane had no effect on membrane current in the absence of GABA. The dose‐response data for potentiation by racemic isoflurane could be fitted with a Hill equation with an EC50 = 320 ± 20 μm isoflurane and a Hill coefficient of h = 2.7 ± 0.4 (means ± s.e.mean).
The potentiations produced by the optical isomers of isoflurane at 2 μm GABA were stereoselective at moderate and high anaesthetic concentrations. The maximum stereoselectivity, about two fold, occurred at the EC50 concentration for general anaesthesia (310 μm isoflurane), with S(+)‐isoflurane being more effective than R(−)‐isoflurane. At sub‐anaesthetic concentrations, the stereoselectivity was less marked and vanished at the lowest concentration used (77 μm isoflurane).
The sustained residual current remaining after exposure of neurones to a desensitizing concentration of GABA (300 μm) was inhibited non‐stereoselectively, but only at high concentrations of isoflurane. The ratio of inhibitions by S(+)‐ and R(−)‐isoflurane (mean ± s.e.mean) was 1.14 ± 0.21 at 770 μm isoflurane. At the EC50 concentration for general anaesthesia, however, the inhibition was barely significant.
The above results are discussed in relation to the possible role of the GABAA receptor channel in general anaesthesia.
Acutely dissociated cerebellar Purkinje neurones from 8–14 day old rats were studied under voltage clamp in the whole‐cell patch‐clamp configuration. Cl− currents induced by bath application of γ‐aminobutyric acid (GABA) were measured (using symmetrical Cl− solutions) at both low (2 μm) non‐desensitizing and high (300 μm) desensitizing concentrations of GABA.
At 2 μm GABA, the bicuculline‐sensitive Cl− currents were potentiated by racemic isoflurane and both of its optical isomers. Isoflurane had no effect on membrane current in the absence of GABA. The dose‐response data for potentiation by racemic isoflurane could be fitted with a Hill equation with an EC50 = 320 ± 20 μm isoflurane and a Hill coefficient of h = 2.7 ± 0.4 (means ± s.e.mean).
The potentiations produced by the optical isomers of isoflurane at 2 μm GABA were stereoselective at moderate and high anaesthetic concentrations. The maximum stereoselectivity, about two fold, occurred at the EC50 concentration for general anaesthesia (310 μm isoflurane), with S(+)‐isoflurane being more effective than R(−)‐isoflurane. At sub‐anaesthetic concentrations, the stereoselectivity was less marked and vanished at the lowest concentration used (77 μm isoflurane).
The sustained residual current remaining after exposure of neurones to a desensitizing concentration of GABA (300 μm) was inhibited non‐stereoselectively, but only at high concentrations of isoflurane. The ratio of inhibitions by S(+)‐ and R(−)‐isoflurane (mean ± s.e.mean) was 1.14 ± 0.21 at 770 μm isoflurane. At the EC50 concentration for general anaesthesia, however, the inhibition was barely significant.
The above results are discussed in relation to the possible role of the GABAA receptor channel in general anaesthesia.
DOI: 10.1111/j.1476-5381.1994.tb13166.x
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