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Possible Mechanism of Dantrolene Stabilization of Cultured Neuroblastoma Cell Plasma Membranes
Author(s) -
Hayashi Teruo,
Kagaya Ariyuki,
Motohashi Nobutaka,
Yamawaki Shigeto
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63051849.x
Subject(s) - dantrolene , mechanism (biology) , membrane , chemistry , biophysics , plasma , cell , microbiology and biotechnology , biochemistry , biology , calcium , philosophy , physics , epistemology , quantum mechanics , organic chemistry
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 Ca 2+ influx, which was reduced to 14% by the absence of external Ca 2+ . Dantrolene inhibited the C48/80‐induced increase in Ca 2+ permeability of plasma membranes in a concentration‐dependent manner (0.33–10 µ M , IC 50 value was 5 µ M ). We next examined C48/80‐induced changes in structural and dynamic membrane properties by electron spin resonance (ESR). The ratio h 0 / 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 µ M ) 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 Ca 2+ . We conclude that dantrolene protects neuroblastoma cell plasma membrane from C48/80‐induced membrane perturbation, which causes Ca 2+ influx and an increase in membrane fluidity. These findings strongly suggest that dantrolene directly stabilizes the neuronal plasma membrane.