title: Possible mechanism of dantrolene stabilization of cultured neuroblastoma cell plasma membranes.
abstract: Some reports have suggested that dantrolene interacts directly with the membrane bilayer. We investigated effects of dantrolene on changes in membrane properties induced by compound 48/80 (C48/80), a membrane stimulator. The addition of C48/80 for 1 min elicited a rapid, dose-dependent Ca2+ influx, which was reduced to 14% by the absence of external Ca2+. Dantrolene inhibited the C48/80-induced increase in Ca2+ permeability of plasma membranes in a concentration-dependent manner (0.33-10 microM, IC50 value was 5 microM). We next examined C48/80-induced changes in structural and dynamic membrane properties by electron spin resonance (ESR). The ratio h0/h-1 was determined to evaluate membrane fluidity. C48/80 increased the membrane fluidity in a concentration-dependent manner (0.1-0.56 mg/ml). Dantrolene (10 microM) itself did not change the membrane fluidity, but it significantly reduced the C48/80-induced increase in membrane fluidity (0.56 mg/ml). Moreover, the C48/80-induced increase in fluidity was dependent on extracellular Ca2+. We conclude that dantrolene protects neuroblastoma cell plasma membrane from C48/80-induced membrane perturbation, which causes Ca2+ influx and an increase in membrane fluidity. These findings strongly suggest that dantrolene directly stabilizes the neuronal plasma membrane.
authors.affiliation: Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Kagaya
authors.forename: N
authors.initials: N
authors.lastname: Motohashi
authors.forename: S
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D003620:Dantrolene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005453:Fluorescence; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D003189:p-Methoxy-N-methylphenethylamine; D014700:Verapamil; D003620:Dantrolene; D002118:Calcium