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 μM 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 μM, 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 μM 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.
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Abbreviations
- AP-5 :
-
(±)-2-amino-5-phosphonopentanoic acid
- AMPA :
-
amino-3-hydroxy-5-methyl-isoxazole-4-propionate
- BSS :
-
balanced salt solution
- CNS :
-
central nervous system
- CICR :
-
Ca2+-induced Ca2+ release
- DCKA :
-
5,7-dichlorokynurenate
- DNasel :
-
deoxyribonuclease I
- DMEM :
-
Dulbecco's Modified Eagle's Medium
- EGTA :
-
ethylene glycol-bis(β-aminoethyl ether)N,N,N′,N′,-tetraacetic acid
- FCS :
-
fetal calf serum
- fura-2-AM :
-
1-(2-(5′-carboxyoxazol-2′-yl)-6-aminobenzofuran-5-oxy-2-ethane-N,N,N′,N′-te-traacetic acid, pentaacetoxymethyl ester
- HEPES :
-
N-[2-hydroxyethyl] piperazine-N′-[2-ethanesulfonic acid]
- [Ca 2+] i :
-
intracellular free Ca2+ concentration
- LTP :
-
long-term potantiation
- MK-801 :
-
(5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]-cyclohepten-5,10-imine hydrogen maleate
- NMDA :
-
N-methyl-D-aspartate
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Hayashi, T., Kagaya, A., Takebayashi, M. et al. Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons. J. Neural Transmission 104, 811–824 (1997). https://doi.org/10.1007/BF01285550
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DOI: https://doi.org/10.1007/BF01285550