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ANESTHETIC PHARMACOLOGY

Activation of Neuronal N-Methyl-D-Aspartate Receptor Channels by Lipid Emulsions

Henry U. Weigt, MD^*, Michael Georgieff, MD^*, Cordian Beyer, PhD, and Karl J. Föhr, PhD^*

*University Clinic of Anesthesiology, Ulm, Germany; and Department of Anatomy and Cell Biology, University of Ulm, Germany

Address correspondence and reprint requests to Karl Föhr, PhD, Universitätsklinikum Ulm, Universitätsklinik für Anästhesie, Steinhövelstraße 9, 89070 Ulm, Germany. Address e-mail to karl.foehr{at}medizin.uni-ulm.de

Lipid emulsions are widely used as carriers for hypnotics such as propofol, etomidate, and diazepam. It is assumed that the emulsions alone exert no effect on cellular functions nor influence the pharmacokinetics, pharmacodynamics, or anesthetic and analgetic potency of the hypnotics they carry. To elucidate possible interactions between lipid emulsions and cell membranes, in particular membrane-bound proteins, we investigated the effects of commercially available lipid emulsions on the cell membranes of cultured cortical neurons from the mouse by using the whole-cell configuration of the patch-clamp technique. Of nine lipid emulsions tested, three, i.e., Intralipid^®, Structolipid^®, and, to a much lesser extent, Abbolipid^®, activated membrane currents in the neuronal cells in a dilution-dependent manner. The emulsion-induced currents were not affected by picrotoxin or bicuculline but were inhibited by DL-AP5 and ketamine. The voltage dependence of the currents was influenced by the presence of Mg²⁺ in a way that is typical for currents conducted by N-methyl-D-aspartate receptor channels. We conclude that Intralipid, Structolipid, and Abbolipid activate N-methyl-D-aspartate receptor channels in cortical neurons.

IMPLICATIONS: Lipid emulsions are widely used as carriers for hypnotics such as propofol, etomidate, or diazepam. We tested nine commercially available lipid emulsions and demonstrate that three of them—Intralipid, Structolipid, and Abbolipid—activate NMDA receptor channels in the membranes of cortical neuronal cells.

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