Xenon and its effect on lamina IX neurons
Xenon is a noble gas. Its anesthetic properties have been recognized for almost 60 years. When compared to desflurane’s blood gas partition coefficient of 0.424, xenon’s blood/gas partition coefficient of 0.115 makes it the least soluble anesthetic agent. It may have many attractive properties as an anesthetic, but it is also quite expensive. It cannot be synthesized and is instead extracted from the atmosphere. About 12 years ago, Anesthesiology featured a nice review article on the drug. In this month’s edition of the journal, Dr. Tatsuro Kohno (Associate Professor, Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan) and colleagues analyzed the effect of xenon on spinal ventral horn neurons and published their findings in “Effect of Xenon on Excitatory and Inhibitory Transmission in Rat Spinal Ventral Horn Neurons.” Indeed, minimum alveolar concentration for volatile anesthetics is dependent on lack of movement in response to a noxious stimulus and as such is caused by anesthetic effects on the spinal cord rather than the brain.
For the experiment, the authors removed the lumbosacral segment of the spinal cord of animals, which was then cut into 500-μm transverse slices. Individual neurons were identified and whole cell patch clamp recordings, where a very high-resistance seal is made between a micropipette and a membrane, were made from the large lamina IX neurons. Concentration-response curves were obtained for the agonists α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA), N-methyl-D-aspartate (NMDA), γ-aminobutyric acid (GABA), and glycine on the spinal lamina IX neurons with and without exposure to xenon.
AMPA elicited an inward current. NMDA, GABA, or glycine elicited an outward current. With tetrodotoxin, an inhibitor of presynaptic phenomena, no effect was observed, so the effects seen were postsynaptic. When applied for 5 min, 50% xenon (about 0.31-0.58 MAC) reversibly, albeit modestly, inhibited AMPA peak amplitudes and receptor-mediated excitatory postsynaptic currents (EPSCs). Xenon had no effect on NMDA-induced currents, NMDA receptor-mediated EPSCs, GABA-induced currents, or glycine.
These findings, though modest, might mean that spinal ventral horn neurons are not the site of action for immobilization by xenon. Additional study is needed.