Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons |
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Authors: | T Hayashi A Kagaya M Takebayashi T Oyamada M Inagaki Y Tawara N Yokota J Horiguchi T -P Su S Yamawaki |
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Institution: | (1) Present address: Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Hiroshima, Japan;(2) Unit on Cellular Pathobiology, Molecular Neuropsychiatry Section, Neuroscience Branch, IRP, National Institute on Drug Abuse, NIH, Baltimore, MD, USA |
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Abstract: | Summary Dantrolene has been known to affect intracellular Ca2+ concentration (Ca2+]i) by inhibiting Ca2+ release from intracellular stores in cultured neurons. We were interested in examining this property of dantrolene in influencing the Ca2+]i affected by the NMDA receptor ligands, KCl, L-type Ca2+ channel blocker nifedipine, and two other intracellular Ca2+-mobilizing agents caffeine and bradykinin. Effect of dantrolene on the spontaneous oscillation of Ca2+]i was also examined. Dantrolene in M concentrations dose-dependently inhibited the increase in Ca2+]i elicited by NMDA and KCl. AP-5, MK-801 (NMDA antagonists), and nifedipine respectively reduced the NMDA and KCl-induced increase in Ca2+]i. Dantrolene, added to the buffer solution together with the antagonists or nifedipine, caused a further reduction in Ca2+]i to a degree similar to that seen with dantrolene alone inhibiting the increase in Ca2+]i caused by NMDA or KCl. At 30 M, dantrolene partially inhibited caffeine-induced increase in Ca2+]i whereas it has no effect on the bradykinin-induced change in Ca2+]i. The spontaneous oscillation of Ca2+]i in frontal cortical neurons was reduced both in amplitude and in base line concentration in the presence of 10 M dantrolene. Our results indicate that dantrolene's mobilizing effects on intracellular Ca2+ stores operate independently from the influxed Ca2+ and that a component of the apparent increase in Ca2+]i elicited by NMDA or KCl represents a dantrolene-sensitive Ca2+ release from intracellular stores. Results also suggest that dantrolene does not affect the IP3-gated release of intracellular Ca2+ and that the spontaneous Ca2+ oscillation is, at least partially, under the control of Ca2+ mobilization from internal stores.Abbreviations
AP-5
(±)-2-amino-5-phosphonopentanoic acid
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AMPA
amino-3-hydroxy-5-methyl-isoxazole-4-propionate
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BSS
balanced salt solution
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CNS
central nervous system
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CICR
Ca2+-induced Ca2+ release
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DCKA
5,7-dichlorokynurenate
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DNasel
deoxyribonuclease I
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DMEM
Dulbecco's Modified Eagle's Medium
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EGTA
ethylene glycol-bis( -aminoethyl ether)N,N,N ,N ,-tetraacetic acid
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FCS
fetal calf serum
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fura-2-AM
1-(2-(5 -carboxyoxazol-2 -yl)-6-aminobenzofuran-5-oxy-2-ethane-N,N,N ,N -te-traacetic acid, pentaacetoxymethyl ester
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HEPES
N-2-hydroxyethyl] piperazine-N -2-ethanesulfonic acid]
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Ca
2+]
i
intracellular free Ca2+ concentration
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LTP
long-term potantiation
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MK-801
(5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzoa,b]-cyclohepten-5,10-imine hydrogen maleate
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NMDA
N-methyl-D-aspartate |
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Keywords: | Ca2+-induced Ca2+ release N-methyl-D-aspartate receptor primary cultures of rat frontal cortical neurons intracellular free Ca2+ concentration intracellular Ca2+ stores spontaneous Ca2+ oscillation |
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