Cholesterol perturbing agents inhibit NMDA-dependent calcium influx in rat hippocampal primary culture.
The present study was carried out to investigate the potential involvement of cholesterol-rich membrane microdomains in the mobilization of calcium induced by NMDA-receptors (NMDA-R). We herein provide evidence that agents interfering with plasma membrane cholesterol (namely, filipin and methyl-beta-cyclodextrin (Cdex)) inhibit the NMDA-stimulated influx of calcium in hippocampal cells in culture. Filipin-treated cells maintained their morphology and were able to respond with a calcium influx to high K(+) challenge, whereas Cdex altered both cellular parameters. These results suggest that the NMDA-R can be located in cholesterol-rich membrane microdomains or alternatively that the mechanisms coupling their dynamics in the post-synaptic membrane are dependent on the integrity of the microdomains.
Frank
Claudio
C
Laboratory of Pharmacology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Giammarioli
Anna Maria
AM
Pepponi
Rita
R
Fiorentini
Carla
C
Rufini
Stefano
S
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003505:Cyclodextrins / Q000494:pharmacology*; D005372:Filipin / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005470:Fluorometry / Q000379:methods; D005677:G(M1) Ganglioside / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D021962:Membrane Microdomains / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D016194:Receptors, N-Methyl-D-Aspartate; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D005677:G(M1) Ganglioside; D016202:N-Methylaspartate; D011189:Potassium Chloride; D005372:Filipin; D002784:Cholesterol; D002118:Calcium