Extracellular Mg2+ modulates intracellular Ca2+ in acutely isolated hippocampal CA1 pyramidal cells of the guinea-pig

Using digital imaging microscopy and fluorescent probes, isolated hippocampal CA1 pyramidal neurons of the guinea-pig were used to examine the roles of [Mg2+](o) in regulation of [Ca2+](i) and [Mg2+](i). Low extracellular Mg ([Mg2+](o)) (0.3 mM) significantly increased [Ca2+](i) compared to 1.2 and 4.8 mM [Mg2+](o). In contrast, [Mg2+](i) levels remained relatively constant, irrespective of alterations of [Mg2+](o). The sustained rise in [Ca2+](i) induced by low [Mg2+](o) was reduced 70% by 1 mu M verapamil and 42% by 1 mM Ni2+, and completely abolished by 5 mM Ni2+. The data suggest that [Mg2+](o) regulates [Ca2+](i) in hippocampal neurons, probably by modulating Ca2+ entry via voltage-sensitive Ca2+ channels, which may play important roles in epileptogenesis, memory, learning and brain trauma. Furthermore, the results demonstrate that intracellular Mg2+ concentration does not follow passively the concentration of Mg2+ in the extracellular solution.