Xenon Inhibits Excitatory but Not Inhibitory Transmission in Rat Spinal Cord Dorsal Horn Neurons

Abstract

BackgroundThe molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method.ResultsIn vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist.ConclusionsXenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon.

Xenon-induced inhibition of synchronized bursts in a rat cortical neuronal network

“…This mechanism differs from that of other general anesthetic agents, such as isoflurane and halothane, which activate the inhibitory -aminobutyric acid type-A (GABAA) receptor channels [Franks and Lieb, 1982;1988;Mihic et al, 1997]. Some researchers claimed that Xe molecules strongly inhibit the excitatory N-methyl-D-aspartate (NMDA) receptor channels [Franks et al, 1998;de Sousa et al, 2000;Ma et al, 2002;Nagale et al, 2005], but others suggested the target to be non-NMDA receptor channels [Plested et al, 2004] or both [Dinse et al, 2005;Preckel et al, 2006;Haseneder et al, 2008;Georgiev et al, 2010]. Therefore, several general anesthetic mechanisms of Xe gas are under consideration.…”

Effect of Xenon on Excitatory and Inhibitory Transmission in Rat Spinal Ventral Horn Neurons

“…4 In later studies, xenon blocked both NMDA receptor-mediated and AMPA receptor-mediated synaptic transmission in cultures of mouse embryonic cortical neurons, 5 rodent amygdala, 6 prefrontal cortex, 7 and spinal cord dorsal horn. 7,8 By contrast, xenon had no effect on inhibitory synaptic transmission. 6 -8 Originally, the brain was considered to be the principal effect site of anesthetics and the determiner of the minimum alveolar concentration (MAC) for volatile anesthetics, a common means to express the strength or potency of anesthetics.…”

“…10,11 In the spinal cord, anesthetic actions might result from a combination of a reduction of the sensory transmission of nociceptive signals within the spinal dorsal horn and a suppression of the neuronal activity in the spinal ventral horn. 12 We reported previously that 50% xenon inhibited both NMDA receptor-medicated and AMPA receptor-mediated glutamatergic excitatory transmission via a postsynaptic mechanism in the spinal dorsal horn 8 ; however, xenon's actions in the spinal ventral horn have not yet been clarified. Therefore, the current study investigated the effects of xenon on spinal ventral horn neurons.…”

“…[3][4][5][6][7][8] A study on cultures of rat hippocampal neurons showed that xenon inhibited N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission but not ␣-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptor-mediated synaptic transmission. 4 In later studies, xenon blocked both NMDA receptor-mediated and AMPA receptor-mediated synaptic transmission in cultures of mouse embryonic cortical neurons, 5 rodent amygdala, 6 prefrontal cortex, 7 and spinal cord dorsal horn.…”

Raman spectra measurements on DEPC liposome and cell membrane of living neuron under xenon pressure

“…A third molecular mechanism was proposed as the direct interaction between anesthetic gases and hydrophobic pockets or clefts in proteins, especially integral membrane proteins such as gated-ion channels. 6 Based on the experimental investigations [7][8][9][10][11][12][13][14][15] and molecular simulations, 16 the target ion-channels have been selected. However, a consistent molecular mechanism has not been proposed yet.…”