Calcium signaling in neuronal cells exposed to the munitions compound cyclotrimethylenetrinitramine (RDX)

Ehrich, M; Wu, X; Werre, SR; Major, MA; McCain, WC; Reddy, G

HERO ID

628752

Reference Type

Journal Article

Year

2009

Language

English

PMID

19652196

HERO ID 628752
In Press No
Year 2009
Title Calcium signaling in neuronal cells exposed to the munitions compound cyclotrimethylenetrinitramine (RDX)
Authors Ehrich, M; Wu, X; Werre, SR; Major, MA; McCain, WC; Reddy, G
Journal International Journal of Toxicology
Volume 28
Issue 5
Page Numbers 425-435
Abstract Cyclotrimethylenetrinitramine (RDX) has been used extensively as an explosive in military munitions. Mechanisms for seizure production, seen in past animal studies, have not been described. Increased calcium levels contribute to excitotoxicity, so in this study neuroblastoma cells are loaded with calcium-indicating dye before application of 1.5 µM to 7.5 mM RDX, with fluorescence recorded for 30 cycles of 11 seconds each. The lowest concentration of RDX increases calcium fluorescence significantly above baseline for cycles 2 to 8; millimolar concentrations increase calcium fluorescence significantly above baseline for cycles 2 to 30. Increases in calcium, like those of 200 nM carbachol, are prevented with 10 mM of calcium chelator ethylene glycol-bis(β-aminoethyl ether)-N,N,N,N tetra-acetic acid (EGTA, tetrasodium salt). Calcium channel blocker verapamil (20 µM), Ca2+-ATPase inhibitor thapsigargin (5 µM), and general membrane stabilizer lidocaine (10 mM) partially attenuate carbachol- and RDX-induced increases in calcium, suggesting that RDX transiently increases intracellular calcium by multiple mechanisms.
Doi 10.1177/1091581809340331
Pmid 19652196
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword calcium; carbachol; human neuroblastoma cells; RDX; SH-SY5Y cells
Is Qa No