Journal of Neuroscience, Vol 7, 4145-4158, Copyright © 1987 by Society for Neuroscience
The effects of excitatory amino acids on intracellular calcium in single mouse striatal neurons in vitro
SN Murphy, SA Thayer and RJ Miller
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
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 greater than
or equal to 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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