The effects of excitatory amino acids on intracellular calcium in single mouse striatal neurons in vitro

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Abstract

Using microspectrofluorimetry and the calcium-sensitive dye fura-2, we examined the effect of excitatory amino acids on [Ca2+](i) in single striatal neurons in vitro. N-methyl-D-aspartic acid (NMDA) produced rapid increases in [Ca2+](i). These were blocked by DL-2-amino-5-phosphonovaleric acid (AP5), by Mg2+, by phencyclidine, and by MK801. The block produced by Mg2+ and MK801 could be relieved by depolarizing cells with veratridine. When external Ca2+ was removed, NMDA no longer increased [Ca2+](i). Furthermore, the effects of NMDA were not blocked by concentrations of La3+ that blocked depolarization induced rises in [Ca2+](i). Substitution of Na+(o) by Li+ did not block the effects of NMDA. Concentrations of L-glutamate ≥ 10-6 M also increased [Ca2+](i). The effects of moderate concentrations of glutamate were blocked by AP5 but not by La3+ or by substitution of Na+ by Li+. The effects of glutamate were blocked by removal of external Ca2+ but were not blocked by concentrations of Mg2+ or MK801 that completely blocked the effects of NMDA. The glutamate analogs kainic acid (KA) and quisqualic acid also increased [Ca2+](i). The effects of KA were blocked by removal of external Ca2+ but not by La3+, Mg2+, MK801, or replacement of Na+ by Li+. Although AP5 was able to block the effects of KA partially, very high concentrations were required. These results may be explained by considering the properties of glutamate-receptor-linked ionophores. Excitatory amino acid induced increases in [Ca2+](i) are consistent with the possibility that Ca2+ mediates excitatory amino acid induced neuronal degeneration.

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Murphy, S. N., Thayer, S. A., & Miller, R. J. (1987). The effects of excitatory amino acids on intracellular calcium in single mouse striatal neurons in vitro. Journal of Neuroscience, 7(12), 4145–4158. https://doi.org/10.1523/jneurosci.07-12-04145.1987

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