Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons

Glutamate-induced excitotoxicity has been implicated as an important mechanism underlying a variety of brain injuries and neurodegenerative diseases. Previously we have shown that taurine has protective effects against glutamate-induced neuronal injury in cultured neurons. Here we propose that the primary underlying mechanism of the neuroprotective function of taurine is due to its action in preventing or reducing glutamate-induced elevation of intracellular free calcium, [Ca2+](i). This hypothesis is supported by the following findings. First, taurine transport inhibitors, e.g., guanidinoethyl sulfonate and beta -alanine, have no effect on taurine's neuroprotective function, suggesting that taurine protects against glutamate-induced neuronal damage through its action on the extracellular membranes. Second, glutamate-induced elevation of [Ca2+](i) is reduced to the basal level upon addition of taurine. Third, pretreatment of cultured neurons with taurine prevents or greatly suppresses the elevation of [Ca2+](i) induced by glutamate. Furthermore, taurine was found to inhibit the influx but not the efflux of Ca-45(2+) in cultured neurons. Taurine has little effect on the binding of [H-3]glutamate to the agonist binding site and of [H-3]MDL 105,519 to the glycine binding site of the N-methyl-D-aspartic acid receptors, suggesting that taurine inhibits Ca-45(2+) influx through other mechanisms, including its inhibitory effect on the reverse mode of the Na+/Ca2+ exchangers (Wu et al. [2000] In: Taurine 4: taurine and excitable tissues. New York: Kluwer Academic/Plenum Publishers. p 35-44) rather than serving as an antagonist to the N-methyl-D-aspartic acid receptors. J. Neurosci. Res. 66:612-619, 2001. (C) 2001 Wiley-Liss, Inc.