Xenon incorporated in a lipid emulsion inhibits NMDA receptor channels.

Abstract

Over the past decade hyperpolarized (129)xenon incorporated in lipid emulsions has been studied for the purpose of imaging enhancement in radiology. Xenon (Xe), a NMDA (N-methyl-D-aspartate)-receptor antagonist, has neuroprotective properties even at subanesthetic concentrations. Thus, its intravenous administration for this purpose deserves further evaluation. In this study, we investigated in an in vitro model the effect of Xe, incorporated in a lipid emulsion (Lipofundin MCT(R) 20%), on the NMDA receptor channel of cortical neurons of the mouse. Pulses of 50 micro M of NMDA solution were extracellularly applied to the cells for 10 s, and the elicited membrane currents (I) were recorded while the membrane potential (V) was clamped at -80 mV. Either Lipofundin MCT(R) 20% or aqueous solution was loaded with Xe and applied simultaneously with the NMDA pulses by means of a multibarreled pipette attached to a battery of infusion-pumps. Xenon equilibrated in Lipofundin(R) caused a concentration-dependent and reversible inhibition of NMDA-induced currents (maximal Xe content [Xemax]: 190 micro l ml-1). The inhibitory effect was equivalent compared with the effect of Xe dissolved in aqueous solution (Xemax: 89 micro l ml-1) even though the Xe content of the lipid solution was almost doubled. Further enhancement of the Xe content by saturating both the lipid emulsion and the aqueous solutions with Xe (Xemax: 256 micro l ml-1) did not increase the inhibitory action on NMDA-receptors. The data demonstrate that Xe dissolved in Lipofundin MCT(R) 20% inhibits NMDA-receptors. Lipid emulsions enriched with Xe may serve as a carrier and a reservoir for Xe.