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Propofol modulates phasic and tonic GABAergic currents in spinal ventral horn inter neurones.

Eckle VS1, Rudolph U2, Antkowiak B3, Grasshoff C3.

Br J Anaesth. 2015 Mar;114(3):491-8.

1Experimental Anaesthesiology Section, Department of Anaesthesiology and Intensive Care, Eberhard-Karls-University, Tübingen, Germany [email protected]

2Laboratory of Genetic Neuropharmacology, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, MA, USA.

3Experimental Anaesthesiology Section, Department of Anaesthesiology and Intensive Care, Eberhard-Karls-University, Tübingen, Germany.

 

Abstract

BACKGROUND:

Surgical interventions like skin incisions trigger withdrawal reflexes which require motor neurones and local circuit interneurones in the spinal  ventral horn. This region plays a key role in mediating immobilizing properties of the GABAergic anaesthetic propofol. However, it is unclear how propofol  modulates GABA(A) receptors in the spinal ventral horn and whether tonic  or phasic inhibition is involved.

METHODS:

Organotypic spinal cord tissue slices were prepared from mice. Whole-cell recordings were performed for quantifying effects of propofolon GABA(A) receptor-mediated phasic transmission and  tonic  conductance.

RESULTS:

Propofol increased GABAergic phasic transmission by a prolongation of the decay time constant in a concentration-dependent manner. The amount of the charge transferred per inhibitory post-synaptic current, described by the area under the curve, was significantly augmented by 1 µM propofol (P<0.01). A GABA(A) receptor-mediated tonic current was not induced by 1 µM propofol but at a concentration of 5 µM (P<0.05).

CONCLUSIONS:

Propofol depresses ventral horn interneurones predominantly by phasic rather than by tonic GABA(A) receptor-mediated inhibition. However, the present results suggest that the involvement of a tonic inhibition might contribute to the efficacy of propofol to depress nociceptive reflexes at high concentrations of the anaesthetic.

© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]

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Propofol modulates phasic and tonic GABAergic currents in spinal ventral horn interneurones

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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