Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats.
BACKGROUND
Volatile anaesthetics are widely used agents in clinical anaesthesia, although their mechanism of action is poorly understood. In particular, the dominant molecular mechanisms by which volatile anaesthetics depress spinal neurones and thereby mediate spinal effects such as immobility have recently become a matter of dispute. As GABAA and glycine receptors are potential candidates we investigated the impact of both receptor systems in mediating the depressant effects of isoflurane and enflurane on spinal neurones in rats.


METHODS
The effects of isoflurane and enflurane on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurones in cultured spinal cord tissue slices obtained from embryonic rats (E 14-15).


RESULTS
Isoflurane and enflurane reduced spontaneous action potential firing. Concentrations causing half-maximal effects (isoflurane: 0.17 mM; enflurane: 0.50 mM) were less than EC50-immobility (isoflurane: 0.32 mM; enflurane: 0.62 mM). Effects of isoflurane were mediated by 39% by glycine receptors and 36% by GABAA receptors. The effects of enflurane were mediated 26% by GABAA receptors and 29% by glycine receptors.


CONCLUSIONS
These results demonstrate that the effects of isoflurane and enflurane on GABAA and glycine receptors contribute almost equally to their depressant actions on spinal ventral horn neurones in rats. The fraction of inhibition mediated by both receptor systems differs between specific volatile anaesthetics. Our data argue against the theory that a dominant molecular mechanism accounts for spinal effects of volatile anaesthetics.
Grasshoff
C
C
Experimental Anaesthesiology Section, Department of Anaesthesiology University of Tuebingen, Tuebingen, Germany. christian.grasshoff@uni-tuebingen.de
Antkowiak
B
B
D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004737:Enflurane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D018009:Receptors, Glycine / Q000187:drug effects* / Q000502:physiology; D046509:Tissue Culture Techniques
D018685:Anesthetics, Inhalation; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D004737:Enflurane; D007530:Isoflurane