The intracellular magnesium and calcium concentrations in cultured dorsal root ganglion neurons were measured using a fluorescent Mg2+ indicator, Mag-Fura-2 and a Ca2+ indicator, Fura-2, respectively. The magnesium concentration in the cytoplasm was higher than that in the nuclei at rest; 0.68 +/- 0.10 mM (mean +/- S.E.M., n = 7) in the cytoplasm and 0.11 +/- 0.05 mM in the nucleus. When depolarized by a 60 mM KCl solution, the magnesium concentration increased remarkably in the cytoplasm; 1.52 +/- 0.26 mM (n = 7) in the cytoplasm and 0.25 +/- 0.12 mM in the nucleus. This is in contrast to a Ca2+ increase due to depolarization in which the increase was remarkable also in the nucleus. The Mg2+ response displayed a rapid spontaneous recovery even in the presence of the high K+ solution. The Ca2+ response, on the other hand, accompanied a slow recovery 'plateau'. Simultaneous measurements of Mg2+ and Ca2+ by a double-labeling experiment revealed that the Ca2+ concentration started to rise 0.46 +/- 0.05 s (n = 32) earlier, and it reached its peak 1.38 +/- 0.12 s (n = 32) earlier than Mg2+. These results support the scheme of 'calcium induced magnesium release', that the depolarization-induced elevation of the Ca2+ concentration causes an increase in the Mg2+ concentration in the cytoplasm. (C) 1999 Elsevier Science B.V. All rights reserved.