Lipid emulsions reduce NMDA-evoked currents.
Membrane currents conducted by the NMDA receptor channels were investigated in cultured cortical neurons and TsA cells transfected with NR1-1a/NR2A subunits of the NMDA receptor. The whole-cell recording technique was used. Current transients evoked by bath application of NMDA for 5 s were characterized by a fast peak and a slow decay to 46.1 +/-15.5% of the peak level at the end. When NMDA was applied in combination with various lipid emulsions (Intralipid, ClinOleic, Lipofundin or Abbolipid, the NMDA-induced currents were reduced, although this reduction did not affect the fast peak, it did affect the decay phase. The amount of reduction depended on the concentration of the lipids (in the case of Abbolipid diluted at 1:40, the current at the end of the 5-s drug application was approximately 2/3 of control). When Abbolipid was applied 40 s before NMDA, peak and late current were reduced to approximately 2/3. The effect of current reduction was the same at either of the two chosen membrane potentials (-80 and +40 mV) which indicates that the effect was not mediated by contamination of the emulsions with Mg(2+). The current reduction produced by Abbolipid was about the same in native neuronal cells and in TsA cells expressing the NR1-1a/NR2A subunits. The current-reducing effect of the lipid emulsions may add to the anesthetic, analgesic and neuroprotective effects seen with hypnotics administered by way of lipid carriers.
Weigt
Henry
H
Clinic for Anesthesiology, University of Ulm, Steinhövelstrasse 9, 89070 Ulm, Germany. henry.weigt@gmx.de
Georgieff
Michael
M
Beyer
Cordian
C
Georgieff
Eva M
EM
Kuhse
Jochen
J
Föhr
Karl J
KJ
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004655:Emulsions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006801:Humans; D007668:Kidney; D008055:Lipids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014162:Transfection
D004655:Emulsions; D018690:Excitatory Amino Acid Agonists; D008055:Lipids; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate