Nitrous oxide and the inhibitory synaptic transmission in rat dorsal horn neurons.
The analgesic effect of nitrous oxide (N(2)O) is thought to depend on noradrenaline release in the spinal cord following activation of descending inhibitory neurons. In addition to this indirect facilitation of inhibition in the spinal cord, we previously showed direct inhibition of glutamate receptors in dorsal horn neurons by N(2)O. Since general anesthetics could possibly affect excitatory and/or inhibitory components of synaptic transmission, we sought to evaluate the direct effect of N(2)O on inhibitory transmission in spinal cord neurons. Using whole-cell patch-clamp recording from rat transversal spinal cord slices, we investigated the actions of 50% N(2)O and 0.5% isoflurane (both 0.3 rat MAC; minimum alveolar concentration) on exogenously applied gamma-aminobutyric acid (GABA)- and glycine-induced currents in rat dorsal horn lamina II neurons. The amplitudes and integrated areas of GABA- and glycine-induced currents were not significantly affected by N(2)O, but were increased in the presence of isoflurane. N(2)O did not affect the amplitude, frequency or decay time probability distribution of either GABA or glycine receptor-mediated miniature postsynaptic currents. We further sought to determine the effect of N(2)O on focal stimulation-evoked synaptic currents mediated by GABA and glycine receptors, and found no effect in the majority of neurons. These and other findings suggest that N(2)O has a discrete action in the spinal cord, distinct from the effects of the volatile anesthetics, consisting of inhibition of excitation in SG neurons through an action on ionotropic glutamatergic receptors and potentiation of inhibition through the descending noradrenergic system.
Georgiev
Stefan K
SK
Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Chuo ku, Niigata, Japan.
Baba
Hiroshi
H
Kohno
Tatsuro
T
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D009609:Nitrous Oxide / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D018756:GABA Antagonists; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D009609:Nitrous Oxide; D005998:Glycine; D001640:Bicuculline